Thrombosis Journal - Most viewed articles

Heparin-induced thrombocytopenia (HIT) is the most important and most frequent drug-induced, immune-mediated type of thrombocytopenia. It is associated with significant morbidity and mortality if unrecognized. In this review, we briefly discuss the main features of heparin-induced thrombocytopenia, particularly analyzing the most recent advances in the pathophysiology, diagnosis and treatment of this syndrome.

Background: Clopidogrel bisulfate is an antiplatelet agent used to prevent ischaemic events in patients with vascular disease. Current guidelines recommend withholding clopidogrel for 7 days pre-operatively. However these are not based on orthopaedic patients. We therefore decided to survey current orthopaedic practice to see whether this complied with available clinical data.MethodA questionnaire was sent to all orthopaedic consultants in Scotland.Four haematology departments, and the manufacturers, were contacted to ask for their recommendations, and a database search was performed. Results: 140 questionnaires were sent with a 60.7% response. 84.7% of respondents have encountered patients on clopidogrel. Of those, 13.9% did not routinely stop it, and 86.1% stopped it 5–21 days pre-operatively (47.2% at 7 days).45.9% had a unit policy on stopping clopidogrel, and the majority (69.4%) did not consult their haematology department prior to instituting their policy.Increased peri-operative bleeding was the most reported complication (22.6%). However this was only noted in those who stopped clopidogrel greater-than 7 days pre-operatively.Haematology advice ranged from continuing clopidogrel peri-operatively to stopping it 7 days pre-operatively and starting low-molecular-weight-heparin for thrombo-prophylaxis. The manufacturers suggested stopping clopidogrel 7 days pre-operatively. An internet search did not reveal any data on the effect of clopidogrel peri-operatively in orthopaedic patients.DiscussionRecommendations on stopping clopidogrel have evolved from studies conducted on patients undergoing cardio-thoracic surgery. There is no data available on the effect of clopidogrel in orthopaedic practice. Our survey indicates that increased bleeding has not been found in patients who continue clopidogrel peri-operatively.Almost half of respondents complied with current recommendations, stopping clopidogrel 7 days pre-operatively. However there remains a lack of consensus amongst orthopaedic surgeons.Currently elective patients should stop clopidogrel 7 days pre-operatively, and emergency patients should stop clopidogrel on admission, however their operation should not be delayed due to clopidogrel usage.

Background: It is well described that diabetes mellitus is a hypercoagulable state. It is also known that patients with renal dysfunction have impaired platelet aggregation and function. It is not well described how renal dysfunction affects the hypercoagulability associated with diabetes. This post-hoc sub-group analysis compares platelet function, clot structure and thrombin generation time at baseline, and following enoxaparin exposure in three groups of subjects. Methods: 30 total subjects were evaluated in the three groups: Group I: normal controls (n = 10), Group II: subjects with renal dysfunction but without diabetes (n = 13), and Group III: subjects with concomitant diabetes and renal dysfunction (n = 7). For each subject, platelet contractile force (PCF), clot elastic modulus (CEM) and thrombin generation time (TGT) were simultaneously measured in whole blood at baseline, and following increasing enoxaparin antifactor Xa activity exposure. The group means for each parameter were determined and compared using one-way analysis of variance, with post-hoc Tukey-Kramer test. Results: At baseline, subjects in Group III (diabetics with concomitant renal dysfunction) display significantly enhanced platelet activity, as measured by PCF (p = 0.003) and CEM (p = 0.03), relative to the non-diabetic Groups I and II. Subjects in Group II (renal dysfunction without diabetes) had significantly prolonged TGT values relative to controls when the antifactor Xa activity concentration reached 0.5 (p = 0.007), 1.0 (p = 0.005) and 3.0 IU/mL (p < 0.0001), respectively. There were no differences between Group II and Group III with respect to TGT at these antifactor Xa activity concentrations. When the antifactor Xa activity concentration reached 3.0 IU/mL, Groups II and III formed significantly less rigid blood clots (CEM p = 0.003) and also trended toward reduced PCF (p = 0.06) relative to Group I. Conclusion: This hypothesis-generating sub-group analysis suggests that at baseline, patients with concomitant diabetes and renal dysfunction have significantly enhanced platelet activity (PCF), and form more rigid blood clots (CEM) compared to controls and subjects with renal dysfunction but no diabetes. This may suggest that the presence of renal dysfunction does not ameliorate the hypercoagulable state associated with diabetes. Secondly, it appears that subjects with renal dysfunction but without diabetes have an enhanced response to enoxaparin relative to controls.

PurposePlatelet-rich plasma (PRP) is an autologous substance with adhesive properties. We aimed at developing and testing the efficacy of a method for PRP preparation in rabbits.Materials and methodsAn in vitro study was carried out to obtain PRP from forty rabbits and to analyze the number of platelets and type of substance needed to trigger platelet activation. To induce platelet activation, 5%, 10%, 25% and 50% CaCl solutions were used. Then, an in vivo study was performed in twelve rabbits to test PRP adhesiveness in lamellar corneal graft. A control group made up of six rabbits underwent corneal transplantation without using PRP. Results: 5% CaCl was the most effective concentration in activating PRP, with a mean time of 19 minutes. An attached corneal flap was seen 3 months after surgery. A detached corneal button was seen in all controls. Conclusion: Our method was able to produce rabbit-derived PRP with suitable properties for soft tissue adhesion. These results could be useful for researchers of the growing fields of tissue repair and experimental transplantation.

Background and purposeThe relationship of D-dimer and deep-vein thrombosis (DVT) after total knee arthroplasty (TKA) remains controversial. The purpose of this study was to assess the value of D-dimer in the detection of early DVT after TKA. Methods: The measurements of plasma D-dimer level were obtained preoperatively and at day 7 postoperatively in 78 patients undergoing TKA. Ascending venography was performed in 7 to 10 days after surgery. The plasma D-dimer levels were correlated statistically with the venographic DVT. Results: Venographic DVT was identified in 40% of patients. High plasma D-dimer level >2.0 μg/ml was found in 68% of patients with DVT and 45% without DVT (P < 0.05). Therefore, high D-dimer level greater than 2.0 μg/ml showed 68% sensitivity, 55% specificity, 60% accuracy, 50% positive predictive rate and 72% negative predictive rate in the detection of early DVT after TKA. Conclusion: High plasma D-dimer level is a moderately sensitive, but less specific marker in the detection of early of DVT after TKA. Measurement of serum D-dimer alone is not accurate enough to detect DVT after TKA. Venography is recommended in patients with elevated D-dimer and clinically suspected but asymptomatic DVT after TKA.

A 42 year-old male former semi-professional soccer player sustained a right lower extremity popliteal contusion during a soccer game. He was clinically diagnosed with a possible traumatic deep vein thrombosis (DVT), and sent for confirmatory tests. A duplex doppler ultrasound was positive for DVT, and the patient was admitted to hospital for anticoagulation (unfractionated heparin, warfarin). Upon discharge from hospital the patient continued oral warfarin anticoagulation (six months), and the use of compression stockings (nine months). He followed up with his family doctor at regular intervals for serial coagulation measurements, and ultrasound examinations. The patient's only identified major thrombotic risk factor was the traumatic injury. One year after the initial deep vein thrombosis (DVT) the patient returned to contact sport, however he continued to have intermittent symptoms of right lower leg pain and right knee effusion.Athletes can develop vascular injuries in a variety of contact and non-contact sports. Trauma is one of the most common causes of lower extremity deep vein thrombosis (DVT), however athletic injuries involving lower extremity traumatic DVT are seldom reported. This diagnosis and the associated risk factors must be considered during the initial physical examination. The primary method of radiological diagnosis of lower extremity DVT is a complete bilateral duplex sonography, which can be augmented by other methods such as evidence-based risk factor analysis. Antithrombotic medication is the current standard of treatment for DVT. Acute thrombolytic treatment has demonstrated an improved therapeutic efficacy, and a decrease in post-DVT symptoms.There is a lack of scientific literature concerning the return to sport protocol following a DVT event. Athletic individuals who desire to return to sport after a DVT need to be fully informed about their treatment and risk of reoccurrence, so that appropriate decisions can be made.

Background: The true relationship between methylenetetrahydrofolate reductase C677T homozygosity and risk of recurrent spontaneous abortion is unknown, and it is unclear if women with these mutations should be anticoagulated during pregnancy.ObjectivesWe report a series of 8 patients with this issue and review the current literature. Methods: 8 patients (3 of whom were actively pregnant) were referred with histories of spontaneous fetal loss; hypercoaguability work-ups revealed each were homozygous for the MTHFR C677T mutation without other thrombophilias. Results: In the 3 women who have conceived, treatment with LMW heparin during pregnancy led to two full-term births and one additional pregnancy without complication. For the 5 who have not, we recommended treatment with LMW heparin upon conception. Conclusion: We provide evidence to support the relationship between MTHFR C677T mutations and recurrent fetal loss, and to suggest that anticoagulation of these patients during pregnancy can lead to a successful pregnancy outcome.

Venous thromboembolism (VTE) is an important cause of avoidable morbidity and mortality. However, routine prophylaxis for at-risk patients is underused. Recent guidelines issued by an international consensus group, including the International Union of Angiology (IUA), recommend use of low-molecular-weight heparins (LMWHs) for the treatment of acute VTE and prevention of recurrence, and for prophylaxis in surgical and medical patients. This review highlights current inadequacies in the provision of thromboprophylaxis, and considers the clinical implications of the European guidelines on the prevention and treatment of VTE.

Background: Protein C (PC) and protein S (PS) determination is part of the thrombophilia investigation in patients with idiopathic venous thromboembolism (VTE). Based on scarce evidence it is a common notion that PC and PS levels decrease during the acute phase of VTE, necessitating delay of testing and temporary transition from warfarin to low molecular weight heparin. We have previously demonstrated that an abnormal PC or PS result determined within 24 hours of VTE diagnosis and before the initiation of warfarin needs to be repeated for confirmation ≥3 months after starting treatment and ≥14 days after stopping anticoagulation therapy. In the current study, we sought to show that normal PC and PS values determined during the acute phase of VTE are not false negatives. Methods: 99 patients with acute idiopathic VTE who had normal PC and PS determination within the first 24 hours of presentation and who subsequently had their oral anticoagulation discontinued after six months of therapy. PC and PS determinations were repeated ≥6 months after starting treatment and ≥ 14 days after stopping warfarin. Proportions of patients who tested abnormal on the second test were calculated and 95% confidence intervals obtained using the Wilson's score method. Data from a previously published study on patients with abnormal initial tests was included for comparison. Results: None of the 99 patients who had normal PC and PS initially had an abnormal result on repeated testing (0%; 95% CI 0 - 3.7%). Data from the previous study showed that, among patients who initially had abnormal results, 40% (95%CI 35.4-84.8%) were confirmed to have low PC and 63.6% (95%CI 16.8-68.7%) low PS on repeated testing. The difference between proportions was statistically significant (χ2 p-value < 0.001). Conclusion: Our results suggest that PC and PS can be determined during the acute phase of VTE and whereas abnormal results need to be confirmed with repeat testing at a later date, a normal result effectively rules out deficiency with only one test.

Thrombophilia can be defined as a predisposition to form clots inappropriately. Thrombotic events during infancy and childhood are increasingly recognized as a significant source of mortality and morbidity. The predisposition to form clots can arise from genetic factors, acquired changes in the clotting mechanism, or, more commonly, an interaction between genetic and acquired factors. Since the turn of the last century, there has been extensive research focusing on both the genetic and acquired causes of thrombophilia, with particular focus on clotting events in the venous circulation. This review describes clinically relevant aspects of genetic venous thrombophilia, which include well-established, lesser known, and suggested causes of inherited thrombophilias.