JBJS | The Use of Heparin in Patients in Whom a Pulmonary Embolism is Suspected After Total Hip Arthroplasty*

The Journal of Bone & Joint Surgery, Volume 81, Issue 8

Articles | August 01, 1999

The Use of Heparin in Patients in Whom a Pulmonary Embolism is Suspected After Total Hip Arthroplasty*

R. L. LAWTON, M.D., PH.D.†; B. F. MORREY, M.D.†, ROCHESTER, MINNESOTA

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Investigation performed at the Mayo Clinic, Rochester

The Journal of Bone & Joint Surgery. 1999; 81:1063-72

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Abstract

Background: The morbidity and mortality associated with pulmonary embolism are well known, as is the benefit of the use of heparin in patients who have a pulmonary embolism. However, the patterns of heparin use as well as its undesirable effects, especially in patients who have recently had a total hip arthroplasty, have been less well studied. Thus, concern arises regarding the use of heparin in patients who have no firm evidence of a pulmonary embolism. The purpose of the current study was to track the use of heparin and associated orthopaedic complications in patients in whom a pulmonary embolism was suspected after a total hip arthroplasty.Methods: The records of 150 patients in whom a pulmonary embolism had been suspected after a total hip arthroplasty were reviewed retrospectively. The rates of individual complications (such as stroke, infection, and hematoma) and those of groups of complications (such as medical complications, orthopaedic complications, and all complications combined) were recorded and then were stratified according to the treatment (with or without heparin), the presence or absence of pulmonary embolism, and other variables.Results: Thirty-two (47 percent) of sixty-eight patients who were managed with heparin had complications compared with sixteen (20 percent) of eighty-two patients who were not thus managed (p = 0.0006). Specifically, patients who were managed with heparin were more likely to have gastrointestinal bleeding, hematological complications, a loose prosthesis, a hematoma, or an early revision arthroplasty (p < 0.05 for all). With the numbers available, the use of heparin was not found to be significantly associated with an increased risk of death, stroke, or infection at the site of the prosthesis. Interestingly, thirty-one (31 percent) of ninety-nine patients who had ventilation-perfusion scans that demonstrated normal findings or findings indicating a low probability of pulmonary embolism were given heparin before the diagnosis of a pulmonary embolism was excluded, and sixteen (52 percent) of these thirty-one had complications.Conclusions: Given this risk profile, we advise against the use of heparin before the diagnosis of pulmonary embolism is established in patients who have had a total hip arthroplasty. This recommendation is supported by algorithms, in widely read medical texts, pertaining to the use of heparin in patients in whom a pulmonary embolism is suspected.

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Introduction

Introduction | Materials and Methods | Results | Discussion | References

Pulmonary embolism remains a potential problem after total hip arthroplasty^{1,8,15,16,27,38}. Treatment usually includes the intravenous use of heparin to achieve partial thromboplastin times ranging from forty-five to seventy seconds ^17,19. In a study of 399 patients who had a pulmonary embolism, the use of heparin reduced the risk of death from 30 to 2.8 percent⁶.

The diagnosis of pulmonary embolism relies on imaging studies because of the lack of specific associated physical signs and laboratory findings¹¹. It is recommended that treatment not be initiated unless ventilation-perfusion scans show a high probability of pulmonary embolism or there are positive findings on angiography, computed tomography, or magnetic resonance imaging. It should be emphasized that the use of heparin is not advised until the diagnosis of pulmonary embolism has been definitely established, especially after an operation^7,13,25,34. A typical algorithm demonstrating the appropriate sequence of diagnostic tests clearly conveys that the use of heparin is inappropriate before the diagnosis has been made (Fig. 1)³⁴. Similar algorithms and descriptions of this principle are documented clearly in widely read medical texts^7,13,25.

Other authors have advocated the use of heparin if the clinical index of suspicion is high despite the absence of a definitive diagnosis². Thus, physicians disagree about when to use heparin. This issue would be clarified if the patterns of heparin use and associated complications were better understood, especially with regard to patients who have a total hip arthroplasty. If clinicians were more aware of the outcomes of both treatment arms (the use of heparin based on radiographic findings compared with its use based on clinical suspicion), they could choose the more appropriate option.

The documented complications of the use of heparin have been primarily hemorrhagic in all patients (not just those who have had a total hip arthroplasty) who have either deep-vein thrombosis or a pulmonary embolism; the prevalence of hemorrhagic complications was 5 to 32 percent in series ranging from twenty-eight to eighty patients who had a pulmonary embolism that was or was not associated with operative treatment^{5,9,11,12,17,18,22,24,26,31,36,39,40}. In a review of studies of antithrombotic therapy, these rates were 3.5 to five times higher than those for patients who had not received heparin¹⁹. Similar findings were reported in recent studies of patients who had had a total joint arthroplasty^28,30. There are, however, no data that we are aware of regarding the relationship between the intravenous use of heparin and prosthesis-related orthopaedic complications, which are of great importance to orthopaedic surgeons. Such data could prove useful when weighing the risks and benefits of the use of heparin, especially when the diagnosis is uncertain.

Given the paucity of available data, the objectives of the current study were (1) to examine the possible association between the use of heparin and all types of complications in patients in whom a pulmonary embolism was suspected after a total hip arthroplasty and (2) to record how heparin was used compared with a variety of recommended treatment algorithms.

*No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. No funds were received in support of this study.

†Mayo Clinic, 200 First Street S.W., Rochester, Minnesota 55905.

*No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. No funds were received in support of this study.

†Mayo Clinic, 200 First Street S.W., Rochester, Minnesota 55905.

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Algorithm showing the flow of diagnosis (Dx) and treatment, according to the findings on the ventilation-perfusion scan, in patients in whom a pulmonary embolism (PE)³⁴ was suspected.

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Chart showing the numbers and percentages of patients who did or did not have a diagnosis of pulmonary embolism (PE), treatment with heparin, or subsequent complications.

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TABLE I DESCRIPTIVE DATA FOR THE ONE HUNDRED AND FIFTY PATIENTS IN WHOM A PULMONARY EMBOLISM WAS SUSPECTED AFTER TOTAL HIP ARTHROPLASTY*

*The patients were stratified according to diagnosis, treatment with heparin, and complications. †The values in parentheses indicate the percentage of the total series. ‡The values in parentheses indicate the percentage of the total for the subcategory. §P = 0.05.

Category	Total No. of Patients†	Pulmonary Embolism‡		Heparin‡		Complications‡
Yes	No	Yes	No	Yes	No
Gender (no. of patients)
Male	72 (48)	19 (26)	53 (74)	34 (47)	38 (53)	21 (29)	51 (71)
Female	78 (52)	20 (26)	58 (74)	34 (44)	44 (56)	27 (35)	51 (65)
Diagnosis (no. of patients)
Osteoarthritis	97 (65)	26 (27)	71 (73)	47 (48)	50 (52)	27 (28)	70 (72)
Fracture	23 (15)	5 (22)	18 (78)	8 (35)	15 (65)	9 (39)	14 (61)
Congenital dysplasia	11 (7)	6	5	7§	4§	7§	4§
Infection at site of prosthesis	7 (5)	1	6	2	5	3	4
Avascular necrosis	5 (3)	0	5	1	4	0	5
Rheumatoid arthritis	5 (3)	0	5	1	4	1	4
Not available	2 (1)
Type of procedure (no. of patients)
Primary	91 (61)	26 (29)	65 (71)	41 (45)	50 (55)	24 (26)	67 (74)
Revision	59 (39)	13 (22)	46 (78)	27 (46)	32 (54)	25 (42)	34 (58)
Total	150 (100)	39 (26)	111 (74)	68 (45)	82 (55)	49 (33)	101 (67)
Mean age (yrs.)	68	69	69	68	69	68	69
Mean duration of follow-up (mos.)	27	32	26	32	24	31	26

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TABLE I DESCRIPTIVE DATA FOR THE ONE HUNDRED AND FIFTY PATIENTS IN WHOM A PULMONARY EMBOLISM WAS SUSPECTED AFTER TOTAL HIP ARTHROPLASTY*

Category	Total No. of Patients†	Pulmonary Embolism‡		Heparin‡		Complications‡
Yes	No	Yes	No	Yes	No
Gender (no. of patients)
Male	72 (48)	19 (26)	53 (74)	34 (47)	38 (53)	21 (29)	51 (71)
Female	78 (52)	20 (26)	58 (74)	34 (44)	44 (56)	27 (35)	51 (65)
Diagnosis (no. of patients)
Osteoarthritis	97 (65)	26 (27)	71 (73)	47 (48)	50 (52)	27 (28)	70 (72)
Fracture	23 (15)	5 (22)	18 (78)	8 (35)	15 (65)	9 (39)	14 (61)
Congenital dysplasia	11 (7)	6	5	7§	4§	7§	4§
Infection at site of prosthesis	7 (5)	1	6	2	5	3	4
Avascular necrosis	5 (3)	0	5	1	4	0	5
Rheumatoid arthritis	5 (3)	0	5	1	4	1	4
Not available	2 (1)
Type of procedure (no. of patients)
Primary	91 (61)	26 (29)	65 (71)	41 (45)	50 (55)	24 (26)	67 (74)
Revision	59 (39)	13 (22)	46 (78)	27 (46)	32 (54)	25 (42)	34 (58)
Total	150 (100)	39 (26)	111 (74)	68 (45)	82 (55)	49 (33)	101 (67)
Mean age (yrs.)	68	69	69	68	69	68	69
Mean duration of follow-up (mos.)	27	32	26	32	24	31	26

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TABLE II DATA ON THE FORTY-EIGHT PATIENTS WHO HAD COMPLICATIONS

*The findings on ventilation-perfusion scanning are listed according to whether the scan showed a high, intermediate, or low probability of pulmonary embolism.

Case	Gender, Age (yrs.)	Symptoms or Diagnosis Leading to Index Op.	Ventilation- Perfusion Scan*	Pulmonary Embolism or Symptomatic Deep-Vein Thrombosis	Treatment with Heparin	Complications
2	M, 72	Painful primary prosthesis	High	+	+	Gastrointestinal bleeding; admitted to intensive-care unit for chest pain
6	M, 78	Painful primary prosthesis	Low	-	+	Infection (coag.-neg. Staph.); Girdle stone arthroplasty; revision at <10 yrs
7	M, 59	Failed primary prosthesis	Low	-	-	Trochanteric nonunion
12	F, 86	Fracture	High	+	+	Heparin-induced thrombocytopenia, gastrointestinal bleeding, ileus, death
13	M, 38	Congenital dysplasia, failed primary prosthesis	High	+	+	Decreased range of motion, shortening
19	F, 59	Failed primary prosthesis	Low	-	-	Trochanteric nonunion, loose prosthesis
21	M, 44	Painful primary prothesis	Low	-	-	Loose prosthesis; revision at 1 yr.
22	F, 88	Fracture	High-intermed.	+	-	Myocardial infarction, anemia, paroxysmal embolism, death
27	F, 74	Failed primary prosthesis	Low	-	+	Loose femoral compo- nent; revision at < 1 yr.
29	M, 77	Loose primary prosthesis	Low-intermed.	-	-	Infection; débridement
30	F, 86	Fracture	Low	-	-	Nonunion
32	F, 76	Osteoarthritis	Low	-	+	Gastrointestinal bleeding, shortening
34	F, 73	Failed primary prosthesis	Low	-	+	Loose femoral component
35	F, 46	Congenital dysplasia	Low	-	+	Hematoma, vaginal bleeding, anemia
37	F, 84	Fracture	Intermed.	+	- (inferior vena cava filter)	Periprosthetic fracture at 2 mos., death
38	F, 53	Osteoarthritis	High-intermed.	+	+	Subsidence and loosen- ing of femoral com- ponent; revision at <10 yrs.
41	F, 76	Osteoarthritis	Low	-	+	Gastrointestinal bleeding, anemia
43	F, 43	Congenital dysplasia	Intermed.	-	+	Readmitted to hospital because of hematoma and pain; rehabilitation
44	M, 65	Failed primary prosthesis	Intermed.	+	+	Dislocation; revision of acetabular component
45	M, 51	Osteoarthritis	Low	-	+	Infection; revision at <10 yrs
46	F, 82	Fracture	High	+	+	Death due to respiratory failure
55	M, 63	Osteoarthritis	Low	-	-	Dislocation
56	M, 69	Osteoarthritis	Low	-	+	Hematoma; incision and drainage
60	M, 71	Fracture	Low	-	+	Thrombocytopenia
61	F, 70	Failed primary prosthesis	Low	-	+	Hematoma
63	F, 69	Congenital dysplasia	Intermed.	+	+	Shortening, limb-length discrepancy
64	M, 65	Osteoarthritis	Low	-	-	Heterotopic ossification, loose prosthesis; re- vision at 6 yrs.
71	F, 77	Failed primary prosthesis	Low-intermed.	-	+	Unexplained drop in hemoglobin, cerebro- vascular accident
72	F, 72	Failed primary prosthesis	Low	-	+	Failed (loose) prosthesis at 6 mos.; revision at <10 yrs.
93	F, 65	Osteoarthritis	Intermed.	-	+	Shortening
96	F, 88	Fracture	Low	-	+	Hematoma
100	F, 65	Osteoarthritis	Low	-	-	Loose prosthesis; revision at 3 yrs.
103	F, 79	Infection at site of primary prosthesis, congenital dysplasia	Low	-	+	Dislocation; open reduction
105	M, 80	Osteoarthritis	Intermed.	-	+	Heterotopic ossification
109	M, 82	Loose primary prosthesis	Low	-	-	Myocardial infarction, death
114	F, 49	Infection at site of primary pros- thesis, congenital dysplasia	Low	-	-	Infection; revision at <10 yrs.
117	M, 63	Failed primary prosthesis	Low	-	-	Dislocation
120	F, 67	Osteoarthritis	Intermed.	+	+	Hematoma, anemia
122	F, 56	Osteoarthritis	Low	+	+	Wound infection, weakness
123	M, 71	Osteoarthritis	High	+	+	Loose prosthesis, shorten- ing; revision at 8 yrs.
126	F, 73	Infection at site of primary prosthesis	Low	-	-	Infection at site of prosthesis, sepsis
127	F, 70	Rheumatoid arthritis	Low-intermed.	+	+	Pneumonia, respiratory failure, death
128	M, 70	Fracture	Low	-	+	Anemia, heparin-induced thrombocytopenia; loose prosthesis; revision at 5 yrs.
129	M, 55	Congenital dysplasia	High-intermed.	+	+	Loose prosthesis, shorten- ing; revision at 8 yrs.
130	M, 81	Osteoarthritis	High	+	+	Gastrointestinal bleeding, anemia, death
132	M, 51	Osteoarthritis	Low	-	+	Infection at site of pros- thesis, loose prosthesis; revisions at 2, 6, and 7 yrs.
138	F, 49	Congenital dysplasia	Low	-	-	Infection at site of pros- thesis; revision at 6 yrs.
146	M, 63	Failed primary prosthesis	Low	-	-	Dislocation at 1 mo.

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TABLE II DATA ON THE FORTY-EIGHT PATIENTS WHO HAD COMPLICATIONS

*The findings on ventilation-perfusion scanning are listed according to whether the scan showed a high, intermediate, or low probability of pulmonary embolism.

Case	Gender, Age (yrs.)	Symptoms or Diagnosis Leading to Index Op.	Ventilation- Perfusion Scan*	Pulmonary Embolism or Symptomatic Deep-Vein Thrombosis	Treatment with Heparin	Complications
2	M, 72	Painful primary prosthesis	High	+	+	Gastrointestinal bleeding; admitted to intensive-care unit for chest pain
6	M, 78	Painful primary prosthesis	Low	-	+	Infection (coag.-neg. Staph.); Girdle stone arthroplasty; revision at <10 yrs
7	M, 59	Failed primary prosthesis	Low	-	-	Trochanteric nonunion
12	F, 86	Fracture	High	+	+	Heparin-induced thrombocytopenia, gastrointestinal bleeding, ileus, death
13	M, 38	Congenital dysplasia, failed primary prosthesis	High	+	+	Decreased range of motion, shortening
19	F, 59	Failed primary prosthesis	Low	-	-	Trochanteric nonunion, loose prosthesis
21	M, 44	Painful primary prothesis	Low	-	-	Loose prosthesis; revision at 1 yr.
22	F, 88	Fracture	High-intermed.	+	-	Myocardial infarction, anemia, paroxysmal embolism, death
27	F, 74	Failed primary prosthesis	Low	-	+	Loose femoral compo- nent; revision at < 1 yr.
29	M, 77	Loose primary prosthesis	Low-intermed.	-	-	Infection; débridement
30	F, 86	Fracture	Low	-	-	Nonunion
32	F, 76	Osteoarthritis	Low	-	+	Gastrointestinal bleeding, shortening
34	F, 73	Failed primary prosthesis	Low	-	+	Loose femoral component
35	F, 46	Congenital dysplasia	Low	-	+	Hematoma, vaginal bleeding, anemia
37	F, 84	Fracture	Intermed.	+	- (inferior vena cava filter)	Periprosthetic fracture at 2 mos., death
38	F, 53	Osteoarthritis	High-intermed.	+	+	Subsidence and loosen- ing of femoral com- ponent; revision at <10 yrs.
41	F, 76	Osteoarthritis	Low	-	+	Gastrointestinal bleeding, anemia
43	F, 43	Congenital dysplasia	Intermed.	-	+	Readmitted to hospital because of hematoma and pain; rehabilitation
44	M, 65	Failed primary prosthesis	Intermed.	+	+	Dislocation; revision of acetabular component
45	M, 51	Osteoarthritis	Low	-	+	Infection; revision at <10 yrs
46	F, 82	Fracture	High	+	+	Death due to respiratory failure
55	M, 63	Osteoarthritis	Low	-	-	Dislocation
56	M, 69	Osteoarthritis	Low	-	+	Hematoma; incision and drainage
60	M, 71	Fracture	Low	-	+	Thrombocytopenia
61	F, 70	Failed primary prosthesis	Low	-	+	Hematoma
63	F, 69	Congenital dysplasia	Intermed.	+	+	Shortening, limb-length discrepancy
64	M, 65	Osteoarthritis	Low	-	-	Heterotopic ossification, loose prosthesis; re- vision at 6 yrs.
71	F, 77	Failed primary prosthesis	Low-intermed.	-	+	Unexplained drop in hemoglobin, cerebro- vascular accident
72	F, 72	Failed primary prosthesis	Low	-	+	Failed (loose) prosthesis at 6 mos.; revision at <10 yrs.
93	F, 65	Osteoarthritis	Intermed.	-	+	Shortening
96	F, 88	Fracture	Low	-	+	Hematoma
100	F, 65	Osteoarthritis	Low	-	-	Loose prosthesis; revision at 3 yrs.
103	F, 79	Infection at site of primary prosthesis, congenital dysplasia	Low	-	+	Dislocation; open reduction
105	M, 80	Osteoarthritis	Intermed.	-	+	Heterotopic ossification
109	M, 82	Loose primary prosthesis	Low	-	-	Myocardial infarction, death
114	F, 49	Infection at site of primary pros- thesis, congenital dysplasia	Low	-	-	Infection; revision at <10 yrs.
117	M, 63	Failed primary prosthesis	Low	-	-	Dislocation
120	F, 67	Osteoarthritis	Intermed.	+	+	Hematoma, anemia
122	F, 56	Osteoarthritis	Low	+	+	Wound infection, weakness
123	M, 71	Osteoarthritis	High	+	+	Loose prosthesis, shorten- ing; revision at 8 yrs.
126	F, 73	Infection at site of primary prosthesis	Low	-	-	Infection at site of prosthesis, sepsis
127	F, 70	Rheumatoid arthritis	Low-intermed.	+	+	Pneumonia, respiratory failure, death
128	M, 70	Fracture	Low	-	+	Anemia, heparin-induced thrombocytopenia; loose prosthesis; revision at 5 yrs.
129	M, 55	Congenital dysplasia	High-intermed.	+	+	Loose prosthesis, shorten- ing; revision at 8 yrs.
130	M, 81	Osteoarthritis	High	+	+	Gastrointestinal bleeding, anemia, death
132	M, 51	Osteoarthritis	Low	-	+	Infection at site of pros- thesis, loose prosthesis; revisions at 2, 6, and 7 yrs.
138	F, 49	Congenital dysplasia	Low	-	-	Infection at site of pros- thesis; revision at 6 yrs.
146	M, 63	Failed primary prosthesis	Low	-	-	Dislocation at 1 mo.

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TABLE III RATE OF COMPLICATIONS ACCORDING TO STATUS WITH RESPECT TO HEPARIN USE AND PULMONARY EMBOLISM

*The values are given as the number of patients who had complications (numerator) divided by the total number of patients in each cell (denominator). The percentages represent the rate of complications.

	Pulmonary Embolism
Yes	No	Row Total
Heparin
Yes	13/34 (38%)	19/34 (56%)	32/68 (47%)
No	2/5	14/77 (18%)	16/82 (20%)
Column total	15/39 (38%)	33/111 (30%)	48/150 (32%)

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TABLE III RATE OF COMPLICATIONS ACCORDING TO STATUS WITH RESPECT TO HEPARIN USE AND PULMONARY EMBOLISM

	Pulmonary Embolism
Yes	No	Row Total
Heparin
Yes	13/34 (38%)	19/34 (56%)	32/68 (47%)
No	2/5	14/77 (18%)	16/82 (20%)
Column total	15/39 (38%)	33/111 (30%)	48/150 (32%)

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TABLE IV PREVALENCE OF COMPLICATIONS ACCORDING TO WHETHER OR NOT HEPARIN WAS USED

*The values are given as the number of patients, with the percentage in parentheses.†NS = not significant.‡At least one instance of gastrointestinal or vaginal bleeding, anemia, thrombocytopenia, or hematoma.

Complication	Heparin* (N = 68)	No Heparin* (N = 82)	P Value†
Death	4 (6)	3 (4)	NS
Gastrointestinal bleeding	5 (7)	0	0.01
Hematological	8 (12)	1 (1)	0.006
Cerebrovascular accident	1 (1)	1 (1)	NS
Orthopaedic	24 (35)	14 (17)	0.01
Loosening	8 (12)	4 (5)	0.05
Hematoma	6 (9)	0	0.005
Revision less than 10 yrs. postop.	10 (15)	5 (6)	0.03
Infection	4 (6)	4 (5)	NS
Fracture	0	2 (2)	NS
Nonunion	0	3 (4)	NS
Any bleeding or hemorrhage‡	13 (19)	1 (1)	0.0007
Other	15 (22)	5 (6)	0.009

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TABLE IV PREVALENCE OF COMPLICATIONS ACCORDING TO WHETHER OR NOT HEPARIN WAS USED

Complication	Heparin* (N = 68)	No Heparin* (N = 82)	P Value†
Death	4 (6)	3 (4)	NS
Gastrointestinal bleeding	5 (7)	0	0.01
Hematological	8 (12)	1 (1)	0.006
Cerebrovascular accident	1 (1)	1 (1)	NS
Orthopaedic	24 (35)	14 (17)	0.01
Loosening	8 (12)	4 (5)	0.05
Hematoma	6 (9)	0	0.005
Revision less than 10 yrs. postop.	10 (15)	5 (6)	0.03
Infection	4 (6)	4 (5)	NS
Fracture	0	2 (2)	NS
Nonunion	0	3 (4)	NS
Any bleeding or hemorrhage‡	13 (19)	1 (1)	0.0007
Other	15 (22)	5 (6)	0.009

Materials and Methods

Introduction | Materials and Methods | Results | Discussion | References

In order to be included in the study, patients had to have had a total hip arthroplasty performed between 1984 and 1994 and a ventilation-perfusion scan performed within six months postoperatively because of suspicion of a pulmonary embolism. The records of 150 consecutive patients who met these criteria were identified. Demographic data and data pertaining to the preoperative diagnosis were recorded (Table I). We evaluated each record with regard to gender; age; diagnosis; comorbidities; duration of hospitalization; diagnosis of a pulmonary embolism; history of a previous thromboembolism; clinical presentation at the time that the pulmonary embolism was suspected; results of subsequent laboratory tests and other studies, including radiography; whether or not the patient was managed with heparin; complications; and outcome variables (Table II).

Patients were considered to have a pulmonary embolism if they had a ventilation-perfusion scan indicating a high probability of such a diagnosis or if they had a positive finding on a pulmonary angiogram or a high-speed computed tomography scan. Two patients who did not meet these radiographic criteria were included among those who had a pulmonary embolism after being diagnosed by the consulting chest-medicine service.

The patients were stratified according to whether they had received heparin intravenously over a period of more than four hours, complications, a diagnosis of pulmonary embolism or deep-vein thrombosis, and test results (for example, activated partial thromboplastin times and findings on ventilation-perfusion scans), to help to define the relationships between these variables.

We were unsure about how often and why heparin was given before the diagnosis of pulmonary embolism was made. We therefore recorded which patients received heparin and when they received it, with special attention paid to when the radiographic diagnosis was made. We also recorded whether heparin was administered before or in the absence of a diagnosis of pulmonary embolism, as would be the case if the diagnosis was made on the basis of clinical suspicion without radiographic evidence. This method permitted us to compare the outcomes of the use of heparin in situations in which such use was assumed to have been appropriate compared with those in situations in which it was not, according to established algorithms.

Since we did not intend to evaluate the effectiveness of postoperative prophylactic measures, the methods of such prophylaxis were not recorded for each patient. A brief review with consulting staff showed that the methods of prophylaxis varied across surgeons and over time.

Statistical Analysis

All analyses were performed with the use of the Statistical Package for the Social Sciences (SPSS, Chicago, Illinois). Simple descriptive statistics and chi-square tests were used to characterize the sample according to age, gender, preoperative diagnosis, whether or not the patient had received heparin intravenously, complications, and diagnosis of pulmonary embolism. Chi-square analyses were used to compare patients who had received heparin with those who had not, according to a number of dependent variables including the presence or absence of complications, the presence or absence of a diagnosis of pulmonary embolism, and comorbidities. Analysis of variance was used to compare anticoagulation parameters (continuous data) according to the presence or absence of a diagnosis of pulmonary embolism and of complications. Statistical significance was defined as a p value of 0.05 or less.

Results

Introduction | Materials and Methods | Results | Discussion | References

Descriptive data regarding the prevalence of pulmonary embolism, whether or not heparin was used, and the rate of complications according to gender, age, diagnosis, type of procedure, and duration of follow-up were recorded (Table I). On the basis of the numbers available, no differences were detected with regard to any of these three parameters in any subgroup except for patients with congenital dysplasia of the hip, who had a higher rate of complications than expected (p = 0.05) (Tables I and II).

All forty-eight patients who had complications were characterized according to gender, age, preoperative diagnosis, the findings on ventilation-perfusion scans, the presence or absence of a pulmonary embolism or deep-vein thrombosis, whether or not they had received heparin, and complications (Table II).

Of the 150 patients included in this study, all of whom were suspected of having a pulmonary embolism and had had at least one ventilation-perfusion scan, thirty-nine (26 percent) actually were diagnosed as having a pulmonary embolism (Fig. 2 and Table III). Of these thirty-nine, thirty-four (87 percent) were managed with intravenous administration of heparin. Of the 111 patients (74 percent) who did not have a pulmonary embolism, thirty-four (31 percent) received heparin.

Of the sixty-eight patients who received heparin, thirty-two (47 percent) had complications. Of the eighty-two patients who did not receive heparin, sixteen (20 percent) had complications; this difference was significant (p = 0.0006). The relationship between the use of heparin and the prevalence of complications was even more pronounced among patients who did not have a pulmonary embolism. Of the thirty-four patients who did not have a pulmonary embolism and received heparin, nineteen (56 percent) had complications compared with fourteen (18 percent) of the seventy-seven patients who did not have a pulmonary embolism and did not receive heparin (p = 0.0001; Table III). Of the patients who had a pulmonary embolism, thirteen (38 percent) of the thirty-four who received heparin and two of the five who did not had complications.

The extent of heparin use was measured according to several indices of anticoagulation based on the amount of heparin that was administered and the partial thromboplastin time. The thirty-four patients who received heparin and had a pulmonary embolism received approximately twice the total amount of heparin than did the thirty-four patients who received heparin and did not have a pulmonary embolism (114,118 units compared with 61,340 units), had a longer mean period of infusion (118 hours compared with sixty-seven hours), and achieved a therapeutic level for a longer mean duration (5.9 days compared with 3.4 days).

In order to better understand the process of heparin treatment and to focus on another concern of this study, that of treatment in the absence of a firm diagnosis, the patients who had normal findings indicating a low probability of pulmonary embolism on ventilation-perfusion scans were assessed. Of the ninety-nine patients who had such findings, thirty-one (31 percent) received heparin and sixty-eight (69 percent) did not, with complications occurring in sixteen (52 percent) of the thirty-one who received heparin and in thirteen (19 percent) of the sixty-eight who did not. Of the thirty-one patients who received heparin and had a normal ventilation-perfusion scan or one indicating a low probability of pulmonary embolism, eight had subsequent evidence of deep-vein thrombosis or pulmonary embolism, or both, according to Doppler ultrasonography, venography, computed tomography, or pulmonary angiography. The remaining twenty-three patients (74 percent) either had a negative result on at least one of these tests or had no additional testing; however, they still were managed with heparin.

The types and frequencies of complications were recorded (Table IV). The use of heparin was associated with a significantly increased risk of gastrointestinal bleeding (p = 0.01), hematological problems (p = 0.006), and orthopaedic complications (p = 0.01). When the orthopaedic complications (loosening of the prosthesis, hematoma, a revision less than ten years after the index procedure, infection, fracture, and nonunion) were considered separately, several were found to be significantly associated with the use of heparin (Table IV). The patients who received heparin had a higher rate of prosthetic loosening than did those who did not receive heparin (eight [12 percent] of sixty-eight compared with four [5 percent] of eighty-two; p = 0.05). The use of heparin also was associated with an increased rate of revision within ten years (ten [15 percent] of sixty-eight compared with five [6 percent] of eighty-two; p = 0.03). Additionally, the use of heparin was associated with formation of a hematoma (six [9 percent] of sixty-eight patients compared with none of eighty-two; p = 0.005). Other complications, including heterotopic ossification, a decreased range of motion, and weakness, when grouped together, were more prevalent in patients who received heparin than in those who did not (fifteen [22 percent] of sixty-eight compared with five [6 percent] of eighty-two; p = 0.009) (Table IV). We did not detect an association between the use of heparin and the rates of death, stroke, fracture, nonunion, or infection at the site of the prosthesis (even when the variable of preoperative infection was statistically controlled). Other complications, such as retroperitoneal hemorrhage, subdural hematoma, and hemothorax, were not observed in this study.

Discussion

Introduction | Materials and Methods | Results | Discussion | References

As with any treatment, physicians must balance the relative risks and benefits of the use of heparin. Obviously, a physician would not intentionally expose a patient to the risks of a treatment if there were no benefit to be gained, as would be the case if a patient who was treated did not actually have the presumed diagnosis. The importance of this point increases with the known risks of the treatment.

Given this context and the fact that no studies, to our knowledge, have assessed the patterns of heparin use or its effects on patients who had had a total hip arthroplasty, we sought to record how heparin was used and to examine its possible association with complications in patients in whom a pulmonary embolism was suspected after a total hip arthroplasty. We identified three important findings in this study.

First, we found that the use of heparin is a risk factor for complications. Heparin was associated with an increased risk of bleeding and other hematological conditions in both the current study and in earlier series ranging from eleven to 100 patients^{9,12,24,33,36,40}. Heparin also was related to a newly defined group of complications specific to patients who had had a total hip arthroplasty. These complications included prosthetic loosening (eight [12 percent] of sixty-eight patients who received heparin compared with four [5 percent] of eighty-two who did not) and early revision (ten [15 percent] of sixty-eight patients who received heparin compared with five [6 percent] of eighty-two who did not). When all complications are grouped together, the highest rate occurred in patients who did not have a pulmonary embolism and who received heparin (Table III).

The relationship between heparin and hematological complications has been well established in previous studies. There have been several trials involving patients who had an angiographically proved pulmonary embolism that was or was not associated with operative treatment; these studies focused primarily on hematological complications of heparin, most commonly bleeding^{9,12,24,33,36,40}. The prevalence of complications was approximately 30 percent in series ranging from twenty-eight to 100 patients; these complications included bleeding at the operative site, in the retroperitoneum, and in the gastrointestinal and urogenital tracts. A finding related specifically to the present study was reported by Salzman et al., who stated that 26 percent of patients who originally were diagnosed as having a pulmonary embolism actually had been misdiagnosed and thus had been managed inappropriately with heparin³³. The use of heparin in the early postoperative period has been associated with an increased risk of bleeding²⁸. Close temporal proximity to an operative procedure has been mentioned as a contraindication to the use of heparin¹⁹.

We are aware of two studies that specifically examined the use of heparin in patients who had had a total joint arthroplasty. Patterson et al. retrospectively reviewed the results for 112 patients who had had intravenous administration of heparin for the treatment of deep-vein thrombosis or a pulmonary embolism after a total joint arthroplasty²⁸. Deep-vein thrombosis was diagnosed with the use of venography, and pulmonary embolism was diagnosed with the use of ventilation-perfusion scanning or angiography, or both. Thirty percent of the patients had a bleeding complication; this rate increased to 45 percent if the use of heparin was initiated before the sixth day after the operation. Forty-eight complications occurred in forty-one patients, with twenty-nine (60 percent) of these complications (in 26 percent of the 112 patients) consisting of bleeding at the operative site. The next-most-common types of complications, in descending order, included gastrointestinal bleeding, thrombocytopenia, prolonged wound drainage, heparin-induced thrombocytopenia, sciatic palsy from a compressive hematoma, and superficial wound infection. Pence and Spencer documented similar types and rates of complications in twenty-one patients who had had a total joint arthroplasty³⁰.

We are not aware of any data in the literature documenting either the effects of treatment with heparin on orthopaedic-related complications, such as those affecting the function of the prosthesis, or the possible mechanisms that could explain the higher rates of loosening or failure among patients managed with heparin. Therefore, it is premature to speculate about the processes affecting such complications in the current study. However, related topics have been addressed in the literature, and those studies may provide insight into the mechanisms that might be at play. For example, laboratory models have shown that possible mechanisms may include bleeding at the bone-cement interface²¹, bleeding-related lamination between the cement and prosthetic interfaces, weakened fixation³, bone resorbtion²³, interposition of tissue³⁷, and formation of a fibrous membrane around the femoral component³⁷. It should be noted that little is known regarding postoperative bleeding at the site of insertion of the cement (after the cement has cured), the effects of bleeding on prostheses inserted without cement, or the in vivo effects on follow-up of patients who have had a total hip arthroplasty and have received heparin.

The second major finding of our study was that the use of heparin before a pulmonary embolism had been diagnosed or ruled out was associated with higher rates of complications. Heparin often is given before a pulmonary embolism has been diagnosed on the basis of definitive testing, including ventilation-perfusion scanning, angiography, or emerging modalities such as high-speed computed tomography. This practice appears to be based on a clinical index of suspicion and leads to the use of heparin in some patients who have a pulmonary embolism but also in many who do not. The use of heparin before a diagnosis has been established may not be far from routine practice despite the fact that many prominent medical sources have recommended against it^7,13,25,34. We recognize that physicians frequently base the decision to use heparin on clinical suspicion. This practice, although expedient, especially when radiographic tests such as ventilation-perfusion scans are not immediately available, places patients in jeopardy of heparin-associated complications.

Given the high rates of heparin-associated complications identified in previous studies and in the current one, physicians might consider treatments other than the intravenous administration of heparin for patients who have a pulmonary embolism. Wolf et al. suggested that, if the patient is doing well clinically despite a diagnosis of pulmonary embolism, then treatment with Coumadin (warfarin) may supplant the intravenous use of heparin⁴². The use of an inferior vena cava filter is another option and is recommended when there is a contraindication to or a complication of anticoagulant therapy in a patient who is at high risk for proximal deep-vein thrombosis or a pulmonary embolism. It is also recommended for the treatment of a thromboembolism that recurs despite adequate anticoagulation^19,41. Rates of patency of 95 percent have been reported^14,20,32,35. The rates of complications have ranged from 1.5 to 9.0 percent⁴, and the problems have included caval thrombus, migration, and penetration of the inferior vena cava^{10,29,31,32,35}.

Our third major finding was that patients in whom a pulmonary embolism was suspected were at risk for complications. Complications occurred at a notable rate in the current study (forty-eight [32 percent] of the entire sample of 150). Even when heparin was not used, complications were common, occurring in sixteen (20 percent) of eighty-two patients (Fig. 2 and Table III). This surprisingly high rate may be explained by the comorbidity profile of this population of patients, who tended to be older (mean age, sixty-eight years) and sicker (ninety-two [61 percent] of the 150 patients had at least one cardiopulmonary or systemic disease, such as a malignant tumor, coronary-artery disease, or diabetes). Patients who have this comorbidity profile could plausibly have postoperative symptoms that, although due to another cause such as preoperative cardiac disease, would arouse suspicion of a pulmonary embolism. These symptoms, interpreted as possible indicators of pulmonary embolism, could in turn have led to the performance of a ventilation-perfusion scan and thus have triggered the criteria for inclusion in the current study. The criterion of a ventilation-perfusion scan performed within six months after the total hip arthroplasty could serve to bias selection toward patients who have cardiovascular premorbid conditions, and these conditions could predispose toward symptoms leading to suspicion of a pulmonary embolism.

In conclusion, the current study shows that the use of heparin increases the risk of bleeding in patients in whom a pulmonary embolism is suspected after a total hip arthroplasty. More importantly for the orthopaedic surgeon, previously unreported data revealed an increased risk of prosthetic loosening, early revision, and other orthopaedic complications in patients who received heparin. These complications were most frequent among patients who did not have a pulmonary embolism but had received heparin. Our findings support the use of more prudent patterns of heparin use, with treatment following a diagnosis rather than a clinical suspicion of pulmonary embolism. Although algorithms in widely read medical texts recommend the establishment of a radiographic diagnosis of pulmonary embolism before the use of heparin is initiated^7,13,25,34, these algorithms frequently have not been followed. Since some of the patients who received heparin did not have a diagnosis of pulmonary embolism, they had an increased likelihood of heparin-associated complications. There is some scant evidence suggesting that heparin may alter the normal bone-cement-prosthesis interface, but, overall, the mechanisms are not well understood.

References

Introduction | Materials and Methods | Results | Discussion | References

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Algorithm showing the flow of diagnosis (Dx) and treatment, according to the findings on the ventilation-perfusion scan, in patients in whom a pulmonary embolism (PE)³⁴ was suspected.

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Chart showing the numbers and percentages of patients who did or did not have a diagnosis of pulmonary embolism (PE), treatment with heparin, or subsequent complications.

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TABLE I DESCRIPTIVE DATA FOR THE ONE HUNDRED AND FIFTY PATIENTS IN WHOM A PULMONARY EMBOLISM WAS SUSPECTED AFTER TOTAL HIP ARTHROPLASTY*

Category	Total No. of Patients†	Pulmonary Embolism‡		Heparin‡		Complications‡
Yes	No	Yes	No	Yes	No
Gender (no. of patients)
Male	72 (48)	19 (26)	53 (74)	34 (47)	38 (53)	21 (29)	51 (71)
Female	78 (52)	20 (26)	58 (74)	34 (44)	44 (56)	27 (35)	51 (65)
Diagnosis (no. of patients)
Osteoarthritis	97 (65)	26 (27)	71 (73)	47 (48)	50 (52)	27 (28)	70 (72)
Fracture	23 (15)	5 (22)	18 (78)	8 (35)	15 (65)	9 (39)	14 (61)
Congenital dysplasia	11 (7)	6	5	7§	4§	7§	4§
Infection at site of prosthesis	7 (5)	1	6	2	5	3	4
Avascular necrosis	5 (3)	0	5	1	4	0	5
Rheumatoid arthritis	5 (3)	0	5	1	4	1	4
Not available	2 (1)
Type of procedure (no. of patients)
Primary	91 (61)	26 (29)	65 (71)	41 (45)	50 (55)	24 (26)	67 (74)
Revision	59 (39)	13 (22)	46 (78)	27 (46)	32 (54)	25 (42)	34 (58)
Total	150 (100)	39 (26)	111 (74)	68 (45)	82 (55)	49 (33)	101 (67)
Mean age (yrs.)	68	69	69	68	69	68	69
Mean duration of follow-up (mos.)	27	32	26	32	24	31	26

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TABLE I DESCRIPTIVE DATA FOR THE ONE HUNDRED AND FIFTY PATIENTS IN WHOM A PULMONARY EMBOLISM WAS SUSPECTED AFTER TOTAL HIP ARTHROPLASTY*

Category	Total No. of Patients†	Pulmonary Embolism‡		Heparin‡		Complications‡
Yes	No	Yes	No	Yes	No
Gender (no. of patients)
Male	72 (48)	19 (26)	53 (74)	34 (47)	38 (53)	21 (29)	51 (71)
Female	78 (52)	20 (26)	58 (74)	34 (44)	44 (56)	27 (35)	51 (65)
Diagnosis (no. of patients)
Osteoarthritis	97 (65)	26 (27)	71 (73)	47 (48)	50 (52)	27 (28)	70 (72)
Fracture	23 (15)	5 (22)	18 (78)	8 (35)	15 (65)	9 (39)	14 (61)
Congenital dysplasia	11 (7)	6	5	7§	4§	7§	4§
Infection at site of prosthesis	7 (5)	1	6	2	5	3	4
Avascular necrosis	5 (3)	0	5	1	4	0	5
Rheumatoid arthritis	5 (3)	0	5	1	4	1	4
Not available	2 (1)
Type of procedure (no. of patients)
Primary	91 (61)	26 (29)	65 (71)	41 (45)	50 (55)	24 (26)	67 (74)
Revision	59 (39)	13 (22)	46 (78)	27 (46)	32 (54)	25 (42)	34 (58)
Total	150 (100)	39 (26)	111 (74)	68 (45)	82 (55)	49 (33)	101 (67)
Mean age (yrs.)	68	69	69	68	69	68	69
Mean duration of follow-up (mos.)	27	32	26	32	24	31	26

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TABLE II DATA ON THE FORTY-EIGHT PATIENTS WHO HAD COMPLICATIONS

*The findings on ventilation-perfusion scanning are listed according to whether the scan showed a high, intermediate, or low probability of pulmonary embolism.

Case	Gender, Age (yrs.)	Symptoms or Diagnosis Leading to Index Op.	Ventilation- Perfusion Scan*	Pulmonary Embolism or Symptomatic Deep-Vein Thrombosis	Treatment with Heparin	Complications
2	M, 72	Painful primary prosthesis	High	+	+	Gastrointestinal bleeding; admitted to intensive-care unit for chest pain
6	M, 78	Painful primary prosthesis	Low	-	+	Infection (coag.-neg. Staph.); Girdle stone arthroplasty; revision at <10 yrs
7	M, 59	Failed primary prosthesis	Low	-	-	Trochanteric nonunion
12	F, 86	Fracture	High	+	+	Heparin-induced thrombocytopenia, gastrointestinal bleeding, ileus, death
13	M, 38	Congenital dysplasia, failed primary prosthesis	High	+	+	Decreased range of motion, shortening
19	F, 59	Failed primary prosthesis	Low	-	-	Trochanteric nonunion, loose prosthesis
21	M, 44	Painful primary prothesis	Low	-	-	Loose prosthesis; revision at 1 yr.
22	F, 88	Fracture	High-intermed.	+	-	Myocardial infarction, anemia, paroxysmal embolism, death
27	F, 74	Failed primary prosthesis	Low	-	+	Loose femoral compo- nent; revision at < 1 yr.
29	M, 77	Loose primary prosthesis	Low-intermed.	-	-	Infection; débridement
30	F, 86	Fracture	Low	-	-	Nonunion
32	F, 76	Osteoarthritis	Low	-	+	Gastrointestinal bleeding, shortening
34	F, 73	Failed primary prosthesis	Low	-	+	Loose femoral component
35	F, 46	Congenital dysplasia	Low	-	+	Hematoma, vaginal bleeding, anemia
37	F, 84	Fracture	Intermed.	+	- (inferior vena cava filter)	Periprosthetic fracture at 2 mos., death
38	F, 53	Osteoarthritis	High-intermed.	+	+	Subsidence and loosen- ing of femoral com- ponent; revision at <10 yrs.
41	F, 76	Osteoarthritis	Low	-	+	Gastrointestinal bleeding, anemia
43	F, 43	Congenital dysplasia	Intermed.	-	+	Readmitted to hospital because of hematoma and pain; rehabilitation
44	M, 65	Failed primary prosthesis	Intermed.	+	+	Dislocation; revision of acetabular component
45	M, 51	Osteoarthritis	Low	-	+	Infection; revision at <10 yrs
46	F, 82	Fracture	High	+	+	Death due to respiratory failure
55	M, 63	Osteoarthritis	Low	-	-	Dislocation
56	M, 69	Osteoarthritis	Low	-	+	Hematoma; incision and drainage
60	M, 71	Fracture	Low	-	+	Thrombocytopenia
61	F, 70	Failed primary prosthesis	Low	-	+	Hematoma
63	F, 69	Congenital dysplasia	Intermed.	+	+	Shortening, limb-length discrepancy
64	M, 65	Osteoarthritis	Low	-	-	Heterotopic ossification, loose prosthesis; re- vision at 6 yrs.
71	F, 77	Failed primary prosthesis	Low-intermed.	-	+	Unexplained drop in hemoglobin, cerebro- vascular accident
72	F, 72	Failed primary prosthesis	Low	-	+	Failed (loose) prosthesis at 6 mos.; revision at <10 yrs.
93	F, 65	Osteoarthritis	Intermed.	-	+	Shortening
96	F, 88	Fracture	Low	-	+	Hematoma
100	F, 65	Osteoarthritis	Low	-	-	Loose prosthesis; revision at 3 yrs.
103	F, 79	Infection at site of primary prosthesis, congenital dysplasia	Low	-	+	Dislocation; open reduction
105	M, 80	Osteoarthritis	Intermed.	-	+	Heterotopic ossification
109	M, 82	Loose primary prosthesis	Low	-	-	Myocardial infarction, death
114	F, 49	Infection at site of primary pros- thesis, congenital dysplasia	Low	-	-	Infection; revision at <10 yrs.
117	M, 63	Failed primary prosthesis	Low	-	-	Dislocation
120	F, 67	Osteoarthritis	Intermed.	+	+	Hematoma, anemia
122	F, 56	Osteoarthritis	Low	+	+	Wound infection, weakness
123	M, 71	Osteoarthritis	High	+	+	Loose prosthesis, shorten- ing; revision at 8 yrs.
126	F, 73	Infection at site of primary prosthesis	Low	-	-	Infection at site of prosthesis, sepsis
127	F, 70	Rheumatoid arthritis	Low-intermed.	+	+	Pneumonia, respiratory failure, death
128	M, 70	Fracture	Low	-	+	Anemia, heparin-induced thrombocytopenia; loose prosthesis; revision at 5 yrs.
129	M, 55	Congenital dysplasia	High-intermed.	+	+	Loose prosthesis, shorten- ing; revision at 8 yrs.
130	M, 81	Osteoarthritis	High	+	+	Gastrointestinal bleeding, anemia, death
132	M, 51	Osteoarthritis	Low	-	+	Infection at site of pros- thesis, loose prosthesis; revisions at 2, 6, and 7 yrs.
138	F, 49	Congenital dysplasia	Low	-	-	Infection at site of pros- thesis; revision at 6 yrs.
146	M, 63	Failed primary prosthesis	Low	-	-	Dislocation at 1 mo.

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TABLE II DATA ON THE FORTY-EIGHT PATIENTS WHO HAD COMPLICATIONS

*The findings on ventilation-perfusion scanning are listed according to whether the scan showed a high, intermediate, or low probability of pulmonary embolism.

Case	Gender, Age (yrs.)	Symptoms or Diagnosis Leading to Index Op.	Ventilation- Perfusion Scan*	Pulmonary Embolism or Symptomatic Deep-Vein Thrombosis	Treatment with Heparin	Complications
2	M, 72	Painful primary prosthesis	High	+	+	Gastrointestinal bleeding; admitted to intensive-care unit for chest pain
6	M, 78	Painful primary prosthesis	Low	-	+	Infection (coag.-neg. Staph.); Girdle stone arthroplasty; revision at <10 yrs
7	M, 59	Failed primary prosthesis	Low	-	-	Trochanteric nonunion
12	F, 86	Fracture	High	+	+	Heparin-induced thrombocytopenia, gastrointestinal bleeding, ileus, death
13	M, 38	Congenital dysplasia, failed primary prosthesis	High	+	+	Decreased range of motion, shortening
19	F, 59	Failed primary prosthesis	Low	-	-	Trochanteric nonunion, loose prosthesis
21	M, 44	Painful primary prothesis	Low	-	-	Loose prosthesis; revision at 1 yr.
22	F, 88	Fracture	High-intermed.	+	-	Myocardial infarction, anemia, paroxysmal embolism, death
27	F, 74	Failed primary prosthesis	Low	-	+	Loose femoral compo- nent; revision at < 1 yr.
29	M, 77	Loose primary prosthesis	Low-intermed.	-	-	Infection; débridement
30	F, 86	Fracture	Low	-	-	Nonunion
32	F, 76	Osteoarthritis	Low	-	+	Gastrointestinal bleeding, shortening
34	F, 73	Failed primary prosthesis	Low	-	+	Loose femoral component
35	F, 46	Congenital dysplasia	Low	-	+	Hematoma, vaginal bleeding, anemia
37	F, 84	Fracture	Intermed.	+	- (inferior vena cava filter)	Periprosthetic fracture at 2 mos., death
38	F, 53	Osteoarthritis	High-intermed.	+	+	Subsidence and loosen- ing of femoral com- ponent; revision at <10 yrs.
41	F, 76	Osteoarthritis	Low	-	+	Gastrointestinal bleeding, anemia
43	F, 43	Congenital dysplasia	Intermed.	-	+	Readmitted to hospital because of hematoma and pain; rehabilitation
44	M, 65	Failed primary prosthesis	Intermed.	+	+	Dislocation; revision of acetabular component
45	M, 51	Osteoarthritis	Low	-	+	Infection; revision at <10 yrs
46	F, 82	Fracture	High	+	+	Death due to respiratory failure
55	M, 63	Osteoarthritis	Low	-	-	Dislocation
56	M, 69	Osteoarthritis	Low	-	+	Hematoma; incision and drainage
60	M, 71	Fracture	Low	-	+	Thrombocytopenia
61	F, 70	Failed primary prosthesis	Low	-	+	Hematoma
63	F, 69	Congenital dysplasia	Intermed.	+	+	Shortening, limb-length discrepancy
64	M, 65	Osteoarthritis	Low	-	-	Heterotopic ossification, loose prosthesis; re- vision at 6 yrs.
71	F, 77	Failed primary prosthesis	Low-intermed.	-	+	Unexplained drop in hemoglobin, cerebro- vascular accident
72	F, 72	Failed primary prosthesis	Low	-	+	Failed (loose) prosthesis at 6 mos.; revision at <10 yrs.
93	F, 65	Osteoarthritis	Intermed.	-	+	Shortening
96	F, 88	Fracture	Low	-	+	Hematoma
100	F, 65	Osteoarthritis	Low	-	-	Loose prosthesis; revision at 3 yrs.
103	F, 79	Infection at site of primary prosthesis, congenital dysplasia	Low	-	+	Dislocation; open reduction
105	M, 80	Osteoarthritis	Intermed.	-	+	Heterotopic ossification
109	M, 82	Loose primary prosthesis	Low	-	-	Myocardial infarction, death
114	F, 49	Infection at site of primary pros- thesis, congenital dysplasia	Low	-	-	Infection; revision at <10 yrs.
117	M, 63	Failed primary prosthesis	Low	-	-	Dislocation
120	F, 67	Osteoarthritis	Intermed.	+	+	Hematoma, anemia
122	F, 56	Osteoarthritis	Low	+	+	Wound infection, weakness
123	M, 71	Osteoarthritis	High	+	+	Loose prosthesis, shorten- ing; revision at 8 yrs.
126	F, 73	Infection at site of primary prosthesis	Low	-	-	Infection at site of prosthesis, sepsis
127	F, 70	Rheumatoid arthritis	Low-intermed.	+	+	Pneumonia, respiratory failure, death
128	M, 70	Fracture	Low	-	+	Anemia, heparin-induced thrombocytopenia; loose prosthesis; revision at 5 yrs.
129	M, 55	Congenital dysplasia	High-intermed.	+	+	Loose prosthesis, shorten- ing; revision at 8 yrs.
130	M, 81	Osteoarthritis	High	+	+	Gastrointestinal bleeding, anemia, death
132	M, 51	Osteoarthritis	Low	-	+	Infection at site of pros- thesis, loose prosthesis; revisions at 2, 6, and 7 yrs.
138	F, 49	Congenital dysplasia	Low	-	-	Infection at site of pros- thesis; revision at 6 yrs.
146	M, 63	Failed primary prosthesis	Low	-	-	Dislocation at 1 mo.

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TABLE III RATE OF COMPLICATIONS ACCORDING TO STATUS WITH RESPECT TO HEPARIN USE AND PULMONARY EMBOLISM

	Pulmonary Embolism
Yes	No	Row Total
Heparin
Yes	13/34 (38%)	19/34 (56%)	32/68 (47%)
No	2/5	14/77 (18%)	16/82 (20%)
Column total	15/39 (38%)	33/111 (30%)	48/150 (32%)

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TABLE III RATE OF COMPLICATIONS ACCORDING TO STATUS WITH RESPECT TO HEPARIN USE AND PULMONARY EMBOLISM

	Pulmonary Embolism
Yes	No	Row Total
Heparin
Yes	13/34 (38%)	19/34 (56%)	32/68 (47%)
No	2/5	14/77 (18%)	16/82 (20%)
Column total	15/39 (38%)	33/111 (30%)	48/150 (32%)

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TABLE IV PREVALENCE OF COMPLICATIONS ACCORDING TO WHETHER OR NOT HEPARIN WAS USED

Complication	Heparin* (N = 68)	No Heparin* (N = 82)	P Value†
Death	4 (6)	3 (4)	NS
Gastrointestinal bleeding	5 (7)	0	0.01
Hematological	8 (12)	1 (1)	0.006
Cerebrovascular accident	1 (1)	1 (1)	NS
Orthopaedic	24 (35)	14 (17)	0.01
Loosening	8 (12)	4 (5)	0.05
Hematoma	6 (9)	0	0.005
Revision less than 10 yrs. postop.	10 (15)	5 (6)	0.03
Infection	4 (6)	4 (5)	NS
Fracture	0	2 (2)	NS
Nonunion	0	3 (4)	NS
Any bleeding or hemorrhage‡	13 (19)	1 (1)	0.0007
Other	15 (22)	5 (6)	0.009

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TABLE IV PREVALENCE OF COMPLICATIONS ACCORDING TO WHETHER OR NOT HEPARIN WAS USED

Complication	Heparin* (N = 68)	No Heparin* (N = 82)	P Value†
Death	4 (6)	3 (4)	NS
Gastrointestinal bleeding	5 (7)	0	0.01
Hematological	8 (12)	1 (1)	0.006
Cerebrovascular accident	1 (1)	1 (1)	NS
Orthopaedic	24 (35)	14 (17)	0.01
Loosening	8 (12)	4 (5)	0.05
Hematoma	6 (9)	0	0.005
Revision less than 10 yrs. postop.	10 (15)	5 (6)	0.03
Infection	4 (6)	4 (5)	NS
Fracture	0	2 (2)	NS
Nonunion	0	3 (4)	NS
Any bleeding or hemorrhage‡	13 (19)	1 (1)	0.0007
Other	15 (22)	5 (6)	0.009