Thrombosis Journal - Most accessed articles

Heparin-induced thrombocytopenia: an update

Massimo Franchini — 2005-10-04T00:00:00Z

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.

Characteristics of ambulatory anticoagulant adverse drug events: a descriptive study

Andrea Long — 2010-02-18T00:00:00Z

Background: Despite the high frequency with which adverse drug events (ADEs) occur in outpatient settings, detailed information regarding these events remains limited. Anticoagulant drugs are associated with increased safety concerns and are commonly involved in outpatient ADEs. We therefore sought to evaluate ambulatory anticoagulation ADEs and the patient population in which they occurred within the Duke University Health System (Durham, NC, USA). Methods: A retrospective chart review of ambulatory warfarin-related ADEs was conducted. An automated trigger surveillance system identified eligible events in ambulatory patients admitted with an International Normalized Ratio (INR) >3 and administration of vitamin K. Event and patient characteristics were evaluated, and quality/process improvement strategies for ambulatory anticoagulation management are described. Results: A total of 169 events in 167 patients were identified from December 1, 2006-June 30, 2008 and included in the study. A median supratherapeutic INR of 6.1 was noted, and roughly half of all events (52.1%) were associated with a bleed. Nearly 74% of events resulted in a need for fresh frozen plasma; 64.8% of bleeds were classified as major. A total of 59.2% of events were at least partially responsible for hospital admission. Median patient age was 68 y (range 36-95 y) with 24.9% initiating therapy within 3 months prior to the event. Of events with a prior documented patient visit (n=157), 73.2% were seen at a Duke clinic or hospital within the previous month. Almost 80% of these patients had anticoagulation therapy addressed, but only 60.0% had a follow-up plan documented in the electronic note. Conclusions: Ambulatory warfarin-related ADEs have significant patient and healthcare utilization consequences in the form of bleeding events and associated hospital admissions. Recommendations for improvement in anticoagulation management include use of information technology to assist monitoring and follow-up documentation, avoid drug interactions, and engage patients in their care.

Clopidogrel in Orthopaedic patients: a review of current practice in Scotland

Jibu Joseph — 2007-05-25T00:00:00Z

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.

Preparation of platelet-rich plasma as a tissue adhesive for experimental transplantation in rabbits

Federico Luengo Gimeno — 2006-09-28T00:00:00Z

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.

Traumatic deep vein thrombosis in a soccer player: A case study

Paul Echlin — 2004-10-14T00:00:00Z

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.

The value of D-dimer in the detection of early deep-vein thrombosis after total knee arthroplasty in Asian patients: a cohort study

Chung-Jen Chen — 2008-05-28T00:00:00Z

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.

Evaluation of the TEG(R)platelet mappingTM assay in blood donors

Louise Bochsen — 2007-02-20T00:00:00Z

Background: Monitoring of antiplatelet therapy in patients at cardiovascular risk is difficult because existing platelet function tests are too sophisticated for clinical routine. The whole blood TEG® Platelet Mapping™ assay measures clot strength as maximal amplitude (MA) and enables for quantification of platelet function, including the contribution of the adenosine diphosphate (ADP) and thromboxane A2 (TxA2) receptors to clot formation. Methods: In 43 healthy blood donors, the analytical (CVa) and inter-individual variability (CVg) of the TEG® Platelet Mapping™ assay were determined together with platelet receptor inhibition in response to arachidonic acid (AA) and ADP. Results: The CVa of the assay for maximal platelet contribution to clot strength (MAThrombin) was 3.5%, for the fibrin contribution to clot strength (MAFibrin) 5.2%, for MAAA 4.5% and for MAADP it was 6.6%. The MAThrombin CVg was 2.8%, MAFibrin 4.7%, MAAA 6.6% and for MAADP it was 26.2%. Females had a higher MAThrombin compared to males (62.8 vs. 58.4 mm, p = 0.005). The platelet TxA2 receptor inhibition was 1.2% (range 0–10%) and lower than for the ADP receptor (18.6% (0–58%); p < 0.0001). Conclusion: The high variability in ADP receptor inhibition may explain both the differences in response to ADP receptor inhibitor therapy and why major bleeding sometimes develops during surgery in patients not treated with ADP receptor inhibitors. An analytical variation of ~5 % for the TEG® enables, however, for routine monitoring of the variability in ADP receptor inhibition and of antiplatelet therapy.

Homocysteine, MTHFR C677T gene polymorphism, folic acid and vitamin B 12 in patients with retinal vein occlusion

Paola Ferrazzi — 2005-09-07T00:00:00Z

Background: Many available data have suggested that hyperhomocysteinaemia, an established independent risk factor for thrombosis (arterial and venous), may be associated with an increased risk of retinal vein occlusion (RVO).Aim of the studyTo evaluate homocysteine metabolism in consecutive caucasian patients affected by RVO from Northern Italy.Patients and Methods69 consecutive patients from Northern Italy (mean age 64.1 ± 14.6 yy) with recent RVO, were tested for plasma levels of homocysteine (tHcy: fasting and after loading with methionine), cyanocobalamine and folic acid levels (CMIA-Abbot) and looking for MTHFR C677T mutation (Light Cycler-Roche) and compared to 50 volunteers, enrolled as a control group. Results: Fasting levels of tHcy were significantly higher in patients than in controls: mean value 14.7 ± 7.7 vs 10.2 ± 8 nmol/ml. Post load levels were also significantly higher: mean value 42.7 ± 23.7 vs 30.4 ± 13.3 nmol/ml; Total homocysteine increase was also evaluated (i.e. Δ-tHcy) after methionine load and was also significantly higher in patients compared to control subjects: mean Δ-tHcy 27.8 ± 21.5 vs 21.0 ± 16 nmol/ml (normal value < 25 nmol/ml). Furthermore, patients affected by RVO show low folic acid and/or vitamin B12 levels, although differences with control group did not reach statistical significance. Heterozygous and homozygous MTHFR mutation were respectively in study group 46% and 29% vs control group 56% and 4%. Conclusion: our data confirm that hyperhomocysteinaemia is a risk factor for RVO, and also that TT genotype of MTHFR C677T is more frequently associated with RVO: if the mutation per se is a risk factor for RVO remains an open question to be confirmed because another study from US did not reveal this aspect.Hyperomocysteinemia is modifiable risk factor for thrombotic diseases. Therefore, a screening for tHcy plasma levels in patients with recent retinal vein occlusion could allow to identify patients who might benefit from supplementation with vitamins and normalization of homocysteine levels, in fasting and after methionine load.

Outcomes of thromboprophylaxis with enoxaparin vs. unfractionated heparin in medical inpatients

Lisa McGarry — 2006-09-27T00:00:00Z

Background: Clinical trials have shown low-molecular weight heparin (LMWH) to be at least as safe and efficacious as unfractionated heparin (UFH) for preventing venous thromboembolism (VTE) in acutely-ill medical inpatients.ObjectiveTo compare clinical and economic outcomes among acutely-ill medical inpatients receiving the LMWH enoxaparin versus UFH prophylaxis in clinical practice. Methods: Using a large, multi-hospital, US database, we identified persons aged ≥40 years hospitalized for ≥6 days for an acute medical condition (including circulatory disorders, respiratory disorders, infectious diseases, or neoplasms) from Q4 1999 to Q1 2002. From these patients, those who received thromboprophylaxis with either enoxaparin or UFH were identified. Surgical patients and those requiring or ineligible for anticoagulation were excluded. We compared the incidence of deep-vein thrombosis (DVT), pulmonary embolism (PE), and all VTE (i.e., DVT and/or PE). Secondary outcomes were occurrence of side-effects, length of hospital stay and total costs. RESULTS: 479 patients received enoxaparin prophylaxis and 2,837 received UFH. The incidence of VTE was 1.7% with enoxaparin prophylaxis versus 6.3% with UFH (RR = 0.26; p < 0.001). Occurrence of side effects, length of stay (10.00 days with enoxaparin vs. 10.26 days with UFH; p = 0.348) and total costs ($18,777 vs. $17,602; p = 0.463) were similar in the 2 groups. Conclusion: We observed a 74% lower risk of VTE among patients receiving enoxaparin prophylaxis versus UFH prophylaxis. There was no significant difference in side effects or economic outcomes. These results provide evidence that the LMWH enoxaparin is more effective than UFH in reducing the risk of VTE in current clinical practice.

A follow-up study of the fate of small asymptomatic deep venous thromboses

Stefan Rosfors — 2010-02-12T00:00:00Z

Background: Postoperative asymptomatic deep venous thromboses (ADVT) can give rise to posttthrombotic syndrome (PTS), but there are still many unresolved issues in this context. For example, there is a lack of knowledge regarding the fate of small ADVT following minor orthopedic surgery. This follow-up study evaluates postthrombotic changes and clinical manifestations of PTS in a group of patients with asymptomatic calf vein DVT after surgery for Achilles tendon rupture. Methods: Forty-six consecutive patients with distal ADVT were contacted and enrolled in a follow-up consisting of a single visit at the hospital at a mean time of 5 years postoperatively, including clinical examination and scoring, ultrasonography and venous plethysmography. All patients had participated in DVT-screening with colour duplex ultrasound (CDU) 3 and 6 weeks postoperatively and 80% of them were treated with anticoagulation. Results: With CDU postthrombotic changes and deep venous reflux were detected at follow-up in more than 50% of the patients, more commonly in somewhat larger calf DVT:s initially affecting more than one vessel. However, only about 10% of the patients had significant venous reflux according to venous plethysmography. No patient had plethysmographic evidence of remaining outflow obstruction, but presence of postthrombotic changes shown with CDU negatively influenced venous outflow capacity measured with plethysmography. A clinical entity of PTS was rarely found and occurred only in two patients (4%) and then classified by Villalta scoring as of mild degree with few clinical signs of disease. Distal ADVT:s detected in the early postoperative period (3 weeks) showed DVT-progression in 75% of the limbs that were still immobilized and without anticoagulation. Conclusions: Asymptomatic postoperative distal DVT:s following surgery for Achilles tendon rupture have a good prognosis and a favourable clinical outcome. In our material of 46 patients the general appearance of the clinical entity of PTS at 5 years follow-up was low (<5%). Morphological and functional abnormalities were mainly seen in those patients that initially had somewhat larger distal DVT:s involving more than one deep calf vein segment.