Post-thrombotic syndrome after total hip or knee arthroplasty ...

Journal of Orthopaedic Surgery 2005;13(2):113-119

Post-thrombotic syndrome after total hip or knee arthroplasty: incidence in patients with asymptomatic deep venous thrombosis OS Schindler Droitwich Knee Clinic, St Andrews Road, Droitwich Spa, Worcestershire, England, United Kingdom

R Dalziel Melbourne Orthopaedic Group, 33 The Avenue, Windsor 3181, Victoria, Australia

ABSTRACT Purpose. To measure the risk of developing signs of post-thrombotic syndrome 15 to 24 months after total hip or knee arthroplasty in patients with asymptomatic deep venous thrombosis (DVT). Methods. A total of 85 total knee arthroplasty patients and 47 total hip arthroplasty patients were postoperatively screened for asymptomatic DVT using colour duplex ultrasound. Results. The rate of asymptomatic DVT was 37.6% (n=32) in knee patients and 34.0% (n=16) in hip patients. All 32 DVT cases in the knee group had thrombi located below the knee, whereas 6 of the 16 DVT cases in the hip group had thrombi located above the knee, the remaining 10 were below the knee. Patients with proximal thrombi were treated with warfarin for 3 months, whereas patients with distal DVT received 300 mg aspirin daily for the same period. All DVT cases were monitored for up to 12 weeks using repeated colour duplex scans. Signs of thrombus resolution were present at around 6 weeks (range, 4– 12 weeks). Clot propagation was observed in 3 cases. In a mean of postoperative 18 months (range, 15–24 months), 28 of the 32 knee patients with asymptomatic DVT were available for follow-up: 11 had transient calf

and ankle swelling, 6 had persistent oedema, and the remaining 11 were symptom free. 14 of the 16 hip patients with asymptomatic DVT were available for follow-up: 6 had transient calf and ankle swelling, 4 had persistent oedema, and 4 remained symptom free. 17 patients reported ongoing problems and were re-examined. Signs of mild-to-moderate postthrombotic syndrome were recorded in 4 knee patients and 3 hip patients. Conclusions. Patients with above-knee DVT were much more likely to have post-thrombotic syndrome. Despite thromboprophylaxis with low-molecularweight heparin, asymptomatic DVT is common after total joint arthroplasty and is responsible for the development of post-thrombotic venous insufficiency and post-thrombotic syndrome in a considerable proportion of patients. Once symptomatic or asymptomatic DVT is established, treatment appears incapable of preventing the occurrence of postthrombotic syndrome, especially in cases of aboveknee DVT. Efforts should hence concentrate on combating DVT propagation and improving DVT prevention. Key words: arthroplasty, replacement, hip; arthroplasty, replacement, knee; postphlebitic syndrome; ultrasonography, Doppler; venous thrombosis; warfarin

Address correspondence and reprint requests to: Mr Oliver Schindler, Droitwich Knee Clinic, St Andrews Road, Droitwich Spa, Worcestershire WR9 8YX, England, United Kingdom. E-mail: [email protected]

Journal of Orthopaedic Surgery

114 OS Schindler and R Dalziel

INTRODUCTION Asymptomatic deep venous thrombosis (DVT) represents one of the most common complications after total joint arthroplasty.1–7 Due to the lack of symptoms, the condition goes mostly unnoticed and, hence, the patient untreated. Little is known about the long-term sequelae arising from asymptomatic DVT, especially its role in the development of post-thrombotic syndrome. Post-thrombotic syndrome comprises a range of clinical signs and symptoms that vary in degree. It is a chronic complication that includes valve damage or outflow obstruction, resulting in vein dilatation and valvular incompetence. 8–11 Information on the incidence of asymptomatic DVT arising as a complication of total joint arthroplasty is scarce in the literature.12 Although problems relating to pulmonary embolism are well-recognised, long-term morbidity resulting from post-thrombotic syndrome continues to be undervalued in clinical practice.13,14 We a i m e d t o m e a s u re t h e l i k e l i h o o d o f developing signs of post-thrombotic syndrome within postoperative 15 to 24 months in patients with asymptomatic DVT after total hip or knee arthroplasty.

distal thrombi received 150 mg of aspirin daily. The treatment period was standardised to 3 months for both groups. All proximal DVTs were monitored with repeated colour duplex scanning at 4-to-6-week intervals. In cases of established popliteal or femoral DVT, patients were assessed using repeated colour duplex scans until definitive signs of clot resolution were present. Within 15 to 24 months (mean, 18 months) after surgery, all patients were followed up with a questionnaire (Table 1) focusing on clinical symptoms and signs associated with the development of post-thrombotic syndrome. Questions were directed towards residual calf or ankle swelling, oedema, pain at rest or during activity, dryness of skin, pigmentation or discolouration of skin, newly developed varicosis, breakdown of skin (ulcera), tingling, or cramps. Patients were allowed to elaborate on any of the symptoms mentioned or on other symptoms that might have developed. Patients who reported symptoms were re-examined. The degree of post-thrombotic syndrome was classified according to criteria defined by the International Consensus Committee on Chronic Venous Disease (Table 2).15 Student’s t test was used for statistical analysis.

RESULTS MATERIALS AND METHODS A total of 132 consecutive patients (61 women and 71 men) with a mean age of 62 years (range, 48–83 years) were included. 85 patients underwent total knee arthroplasty (TKA) and 47 total hip arthroplasty (THA); all received epidural anaesthesia with sedation. In preoperative assessment, both lower extremities were thoroughly examined to exclude signs of venous insufficiency including oedema, varicosis, or trophic skin changes. Patients with apparent signs of postthrombotic syndrome, previous lower-limb DVT, or a history of major lower-limb surgery including joint replacements were excluded. 12 patients, who had undergone uneventful arthroscopic procedures at least 6 months prior to admission, were also included. All patients received low-molecular-weight heparin as prophylaxis, which was administered from postoperative 6 hours until discharge. The mean hospital stay was 7 days (range, 5–12 days). Colour duplex scan was performed 5 to 7 days after surgery. Patients with thrombi were classified by thrombi location: below the popliteal level within the calf veins (distal thrombi), or within the popliteal and femoral veins (proximal thrombi). Patients with proximal thrombi received warfarin, whereas patients with

The overall incidence of asymptomatic DVT occurring within postoperative 7 days was 36.4% (48 patients: 27 female and 21 male)—below the knee in 42 patients and above the knee in 6 patients. Clot propagation was observed in 3 cases, 2 of which originally suffered below-knee DVT. Six patients with below-knee involvement were affected bilaterally. Signs of thrombophlebitis were recorded in 2 patients: one had distal DVT, the other proximal DVT; both later developed signs of post-thrombotic syndrome. No patients receiving warfarin or aspirin had side-effects or complications during the treatment period. Signs of thrombus resolution were recorded postoperatively in a mean of 6 weeks (range, 4–12 weeks). Of the 132 patients, 117 (75 TKA and 42 THA) responded to the questionnaire (response rate, 89%) in postoperative 15 to 24 months. Of the 117 respondents, 42 had previously been affected by asymptomatic DVT. Transient calf or ankle swelling was recorded in 17 of 42 patients with asymptomatic DVT and in 15 of 75 patients without DVT. Persistent oedema was present in 10 of 42 patients with asymptomatic DVT and in one of 75 patients without DVT. Of the 42 patients previously affected by asymptomatic DVT, 17 reported ongoing problems and were re-examined. Seven had developed

Vol. 13 No. 2, August 2005

Post-thrombotic syndrome after TKA or THA in asymptomatic DVT patients 115 Table 1 Questionnaire used to screen for post-thrombotic syndrome

QUESTIONNAIRE 1a. 1b. 2. 3. 4.

5. 6. 7. 8. 9.

I received a Hip replacement Knee replacement Which leg was operated on? Right Left Did you develop a blood clot after your operation? Yes, in my right leg Yes, in my left leg No Did you receive any of the following drugs after your operation? Nothing Aspirin Warfarin Did you develop swelling in your calf or ankle? (tick as many as necessary) Yes, in my right calf Yes, in my left calf No Yes, in my right ankle Yes, in my left ankle No If you had a swollen calf/ankle, what has happened to it since your operation? It increased It stayed the same It decreased It disappeared Do you suffer from activity-related calf pain or muscle cramps? Yes No Did you develop any of the following skin problems in the lower leg? Dry skin Redness Discolouration Varicose veins If you developed any skin problems, when did they appear?................months after surgery Did your skin break down around the ankle? Yes, but it has healed since then Yes, and it still requires treatment No

Table 2 Clinical classification of chronic lower extremity venous disease15

No visible or palpable signs of venous disease Telangiectases, reticular veins, malleolar flare Varicose veins Oedema without skin changes Skin changes ascribed to venous disease (eg pigmentation, venous eczema, lipodermatosclerosis) Class 5 Skin changes as defined above with healed ulceration Class 6 Skin changes as defined above with active ulceration Class 0 Class 1 Class 2 Class 3 Class 4

patients, 28 were available for follow-up: 11 reported transient leg or ankle swelling, 6 presented with chronic lower-leg oedema, the remaining 11 were symptom free. Four patients developed signs of post-thrombotic syndrome: 3 classified as class 2/3 representing mild, and one as class 4 representing moderate. In a mean of postoperative 18 months, the incidence of postthrombotic syndrome in patients affected by asymptomatic DVT was 14.3% (4 out of 28), while the overall incidence of post-thrombotic syndrome in all TKA patients available for follow-up was 5.3% (4 out of 75). Total hip arthroplasty group

objective signs of post-thrombotic syndrome (Table 3). No patient developed overt ulceration within the study period. Total knee arthroplasty group Asymptomatic DVT developed in 32 (37.6%) of 85 patients receiving TKA, with all thrombi located in the calf veins below the popliteal level. Clot propagation into the popliteal vein was noted in one patient, who also developed signs of thrombophlebitis. Of the 32

Asymptomatic DVT developed in 16 (34.0%) of the 47 patients receiving THA: 10 located in the calf veins below the popliteal level, 6 involving the popliteal and femoral veins. Clot propagation was observed in one patient with below-knee DVT and another with aboveknee DVT. Thrombophlebitis developed in one case of above-knee DVT. Of the 16 patients, 14 were available for follow-up: 6 reported transient leg or ankle swelling, 4 presented chronic lower leg oedema, the remaining 4 were symptom free. Three patients developed moderate class-4 post-thrombotic syndrome. In a mean of postoperative 18 months, the



Table 3 Clinical details of patients with post-thrombotic syndrome (PTS)

Patient Sex

* † ‡ §

Age (years)

Joint replaced

Level of DVT*

Follow-up Persistent ExercisePTS signs‡ period calf related (months) swelling calf pain DS/VV/MC Yes No 15 Aspirin OED/DC/VV Yes Yes 23 Warfarin Treat† ment

Grade§ Comments

2 4

1 2

F F

70 64

Right knee Distal Right knee Distal to proximal

3 4 5

M F F

80 81 75

Aspirin Right knee Distal Aspirin Left knee Distal Right hip Proximal Warfarin

16 21 19

Yes Yes Yes

Yes Yes No

DS/OED/MC DS/OED/AS DC/AS/MC

3 3 4

6

F

85

Right hip

Distal to Warfarin proximal

22

No

Yes

DS/DC/VV/MC

4

7

M

65

Right hip

Proximal Warfarin

18

No

No

DS/DC/MC

4

Overt thrombophlebitis, clot propagation (tibial to popliteal) Overt thrombophlebitis Clot propagation (tibial to popliteal) -

DVT denotes deep venous thrombosis; proximal represents femoropopliteal/superficial femoral area and distal below-knee area Aspirin (150 mg/day) or warfarin (international normalised ratio 2.5–3.5) for 3 months DS denotes dry skin, VV varicose veins, MC muscle cramps, OED oedema, DC discolouration, and AS altered sensation According to clinical classification of chronic lower extremity venous disease15

incidence of post-thrombotic syndrome in patients affected by asymptomatic DVT was 21.4% (3 out of 14), while the overall incidence of post-thrombotic syndrome in all THA patients available for followup was 7.1% (3 out of 42).

DISCUSSION DVT is a common complication following total joint arthroplasty, with incidence reported between 30% and 70%, most of which is asymptomatic.1–7,16 Localised and systemic complications can arise from DVT, with pulmonary embolism representing the most devastating systemic thrombo-embolic complication after joint replacement surgery. Nonetheless, the reported mortality rates are low, with a mean incidence of 0.1% to 1.0%.17–19 Localised problems, such as post-thrombotic syndrome, pose a far more common risk to patients with DVT and appear to be underestimated in clinical practice.8,10,13,14 Reported rates of asymptomatic DVT without primary prophylaxis range from 20% to 58%, with 1.5% to 8% detected in the femoral vein. 1,2,5

Despite the administration of primary chemoprophylaxis such as warfarin or aspirin, the incidence of asymptomatic DVT remains high, with reported figures ranging from 34% to 61%, of which 2.5% to 9.1% are located proximally. 3,4,6,7,16 These findings are similar to our results revealing a DVT rate of 37.6% in knee patients and 34.0% in hip patients. There was no significant difference between the 2 groups. The rate of symptomatic DVT following total joint arthroplasty has been reported to be much lower, ranging from 2.1% to 12.5%, with 50% to 85% situated above the knee. 5,20 Once developed, a thrombus can further enlarge and propagate proximally, as occurred in 6.3% of patients with asymptomatic distal DVT in the current study. The occurrence of proximal clot propagation varies and has not been reported; nonetheless, available figures seem to range between 5% and 23%, representing a substantial risk to patients if left untreated.9,21–23 Venography is an invasive, inconvenient, and expensive screening method. It has been associated with risks of allergic reaction, post-venographic phlebitis, and clot propagation. 1,16,24 Although


Post-thrombotic syndrome after TKA or THA in asymptomatic DVT patients 117

many consider it the gold standard, it is impractical to use due to its invasiveness and possible thrombogenic potential, especially for repeated investigations. With sensitivity values between 67% and 91%, and specificity values between 97% and 99%, colour duplex ultrasound has become the assessment tool of choice. 16,25–29 However, the reliability of ultrasound in assessing DVT depends on the experience of the investigator, especially when assessing calf vein thrombi. 1,2,27–29 The recently introduced analysis of D-dimer (a fibrin degeneration product produced during fibrinolysis) has demonstrated a high negative predictive value for DVT30 and may help to further enhance the reliability of DVT diagnosis by reducing the need for imaging studies in cases with negative test results.27,30,31 Of the patients available for follow-up, 4 of 34 with below-knee DVT and 3 of 8 with proximal DVT developed signs of post-thrombotic syndrome. This 16.7% (7 of 42) incidence rate suggests that every sixth patient affected by asymptomatic DVT may be exposed to such long-term complications. The overall risk ratio for developing post-thrombotic syndrome was 1:16. Patients without ultrasonographically proven DVT did not develop post-thrombotic syndrome– related morbidity. Unfortunately, the literature about postthrombotic syndrome is scarce, and the prevalence of post-thrombotic syndrome following a s y m p t o m a t i c D V T re m a i n s u n k n o w n . T h e prevalence of patients suffering symptomatic DVT has been reported between 24% and 70%.8,11,23,32–35 To the best of our knowledge, only one study has been published that comments on the occurrence of post-thrombotic syndrome after asymptomatic postoperative DVT: Siragusa et al. 12 investigated 98 patients undergoing elective orthopaedic procedures and found that 46.9% presented with an asymptomatic DVT postoperatively; 23.9% of these patients subsequently developed signs of postthrombotic syndrome over a period of 2 to 4 years. Although the follow-up period was considerably longer in their study than in the current study, the proportion of patients affected by post-thrombotic syndrome is only slightly higher and, hence, compares favourably with our results. The d e v e l o p m e n t o f p o s t - t h ro m b o t i c s y n d ro m e appears to increase with time, as reported in other studies. 10,35 The findings suggest that symptoms of post-thrombotic syndrome may occur as early as 7 months postoperatively, and that post-thrombotic syndrome generally manifests within 18 to 24 months.10,11,35

Supported by previous studies, 13,14 our results suggest that post-thrombotic syndrome is an underestimated complication following total joint arthroplasty, especially when considering the long-term morbidity associated with postthrombotic syndrome. Furthermore, the economic effects of such complications are considerable. Bergqvist et al. 36 estimated that the additional long-term health-care costs for post-thrombotic complications was approximately 75% of that of primary DVT. Most orthopaedic surgeons do not deal with the presentation, diagnosis, or treatment of complications related to post-thrombotic syndrome; therefore, they are mostly unaware of the suffering of the patients, and consequently undervalue the morbidity related to post-thrombotic syndrome. There are several shortcomings in this study, in particular the subjective nature of the assessment of signs and symptoms relating to the classification of post-thrombotic syndrome, despite the use of established assessment criteria. 15 It would have been desirable to have an extended followup period and also to incorporate a control group of patients with asymptomatic DVT receiving no treatment. Despite thromboprophylaxis and the administration of warfarin and aspirin in cases of asymptomatic DVT, the incidence of post-thrombotic syndrome remains high. The 3 cases of thrombophlebitis in this study went on to develop signs of post-thrombotic syndrome. This raises concern as to whether thrombophlebitis should be considered a precursor of post-thrombotic syndrome. We demonstrated that post-thrombotic syndrome evolving from asymptomatic DVT has to be treated as a far more common complication than previously recognised. Moreover, overt signs of post-thrombotic syndrome may develop as early as 15 to 18 months postoperatively. Further investigations are needed to determine whether DVT surveillance and subsequent instigation of treatment may mitigate the severity of long-term complications related to post-thrombotic syndrome in patients undergoing joint arthroplasty. It appears that once symptomatic or asymptomatic DVT has developed, treatment is incapable of preventing the occurrence of post-thrombotic syndrome. 37,38 Our results suggest that proximal extension of DVT into popliteal and femoral veins increases the likelihood of developing post-thrombotic syndrome by a factor of 5. Hence, efforts should concentrate not only on improvements in combating the propagation of calf DVT, but on DVT prevention in general.


ACKNOWLEDGEMENTS The authors thank Sylvia Louise Davies for reviewing


the manuscript and Dr Peter Bloombury, Consultant Physician of the Avenue Clinic, Melbourne, Australia for his inspiration.

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