Evidence for treatment of muscular vein thrombosis in orthopaedic patients

Background

Does below-knee symptomatic muscular (gastrocnemius or soleus) vein thrombosis (MVT) warrant investigation and treatment in post-operative orthopaedic patients? We performed a literature search and evaluated the evidence looking for guidance regarding this question.

Materials and methods

We performed a literature search with the use of PubMed, Medline and Google Scholar from 1950 to September 2011. Search terms included “muscular vein thrombosis” (MVT) and “isolated gastrocnemius or soleus vein thrombosis” (IGSVT). We reviewed the eight level II studies relevant to our search, only one of which was in a specific orthopaedic population.

Results

Studies looking at the rates of progression of isolated MVT have shown conflicting results. There is also a lack of consensus between studies that compare progression amongst groups with or without anticoagulant treatment. The majority of the studies do not distinguish between medical, surgical or orthopaedic patients.

Conclusions

We cannot confidently recommend commencement of anticoagulation treatment upon identification of MVT in post-operative orthopaedic patients. We can only suggest that, once MVT is diagnosed, the patient should undergo serial ultrasound scan (USS) duplex scans, and if propagation is identified, then treatment may be deemed beneficial.Level of evidence: III (review of non-randomized controlled cohort/follow-up studies).     

Effect of 200 μG/day of vitamin k1 on the variability of anticoagulation control in patients on warfarin: A randomized controlled trial

Background

Controversy exists whether low-dose vitamin K supplementation can improve anticoagulation control in patients with unstable anticoagulation under warfarin. In a single- centre randomized, double-blind, placebo-controlled study, we evaluated the effectiveness of 200 μg/day of vitamin K1 in patients with unstable control under warfarin.

Methods

Effectiveness of Vitamin K1 supplementation was primarily assessed by the percentage (%) of Time-in-Therapeutic-Range (TTR) and secondarily by the standard deviation (SD) of the patient’s INR values; the proportion of out-of-range INRs; and the number of dose changes on warfarin. Their change scores were obtained by subtracting the mean value in the 6 months pre-randomization from the mean value in the 6 months post-randomization. Multivariable linear-regressions identified factors associated with anticoagulation instability.

Results

Fifty out of 54 patients were analyzed (intervention: n = 26; placebo: n = 24). Most indications (87%) for anticoagulation were venous thromboembolism (VTE). The intervention was associated with a greater reduction in the change scores for the SD of INRs between the pre and post-randomization periods compared with placebo. The mean change score was -0.259 ± 0.307 with the intervention and -0.046 ± 0.345 with placebo (p = 0.026). There was no effect on the change scores of the (%) TTR (p = 0.98), the number of INRs out-of-range (p = 0.58) and the number of dose changes (p = 0.604). Factors independently associated with increased variability in the SD of INRs were increased alcoholic drinks/week (p = 0.017), dosing errors (p = 0.0009) and missed INR appointments (p = 0.035).

Conclusion

Vitamin K1 supplementation reduces the SD of INRs as an indicator of the variability in anticoagulation control in patients treated with warfarin for VTE.     

An update on the use of anticoagulant therapy in ST-segment elevation myocardial infarction

Introduction: Together with antiplatelet therapy, anticoagulants are vital to improve outcomes in patients presenting with ST-segment elevation myocardial infarction.

Challenges lie in finding the optimal balance between the risk of bleeding and preventing thrombotic complications such as reinfarction or stent thrombosis. During the last decade, bivalirudin was introduced as a valid alternative to heparin for patients undergoing primary percutaneous coronary intervention. Several trials have been conducted to identify the agent with the best antithrombotic results at the lowest bleeding complication rate. In a rapidly evolving field with changes in vascular access, available P2Y₁₂ inhibitors, and indications for glycoprotein IIb/IIIa inhibitor administration, conflicting evidence became available.

Areas covered: This paper mainly focuses on the evidence above and gives brief discussion to the recent literature on anticoagulation in fibrinolytic therapy and advances in antiplatelet therapy.

Expert opinion: To date, no robust evidence is available challenging unfractionated heparin as the primary choice for anticoagulation in patients presenting with ST-segment elevation myocardial infarction. Further research should include efforts to refine anticoagulation strategies on an individual patient level. For patients undergoing primary percutaneous coronary intervention, bivalirudin could be used as an alternative to unfractionated heparin, while enoxaparin or fondaparinux is an alternative agent for patients treated with fibrinolytic therapy.     

Endocarditis marántica

Marantic endocarditis is characterized by the presence of sterile vegetations in the heart valves, and is associated with hypercoagulability states (cancer, autoimmune diseases, HIV). Its main complications are stroke, pulmonary thromboembolism, acute intestinal ischemia and splenic, renal and hepatic infarcts. We present the case of a 57-year-old patient with a history of uterine neoplasia. She went to the emergency department due to sudden loss of strength in the left side of the body. A computed tomography (CT) scan showed right ischemic stroke, and she underwent endovascular reperfusion and thrombectomy. Four days later, she suffered acute respiratory failure, with angio-CT showing pulmonary thromboembolism. Later, paroxysmal atrial fibrillation and distal ischemia in the second toe of the left foot appeared. She was diagnosed with marantic endocarditis by means of transesophageal echocardiography, and died 72 h later due to multiorgan failure. Early diagnosis and treatment with anticoagulation can reduce the mortality of this disease, since it is underdiagnosed, and often only comes to light during postmortem examination.     

Management of pulmonary embolism

Pulmonary embolism (PE) is a common condition with significant mortality and morbidity. Its occurrence frequently triggers referral to critical care services. Patients within critical care environments are also at elevated risk of developing venous thrombo-embolism and PE. This highlights the need for critical care clinicians to be confident in their approach to the patient with PE. Furthermore, the co-morbid conditions in this patient group may present additional challenges both in diagnosis (e.g. safe access to radiology) and management (e.g. relative contraindication to anticoagulation/thrombolysis in trauma or intracranial haemorrhage). This brief review summarizes the contemporary evidence base regarding both diagnosis and treatment strategies and draws upon this to suggest a simple algorithm for investigation, risk stratification and management, particularly tailored to patients within a critical care setting.     

Management of a COVID-19 Patient during ECMO: Paying Attention to Acquired von Willebrand Syndrome

Patients with severe COVID-19 often experience complications including coagulopathy and fatal thrombosis. COVID-19 pneumonia sometimes leads to acute respiratory distress syndrome, requiring extracorporeal membrane oxygenation (ECMO), during which thrombosis and bleeding are major causes of death. Anticoagulation such as heparin is essential for COVID-19 patients on ECMO; however, bleeding might be caused by not only heparin, but also acquired von Willebrand syndrome (AVWS). To date, no study has examined ECMO-related bleeding and AVWS in COVID-19 patients.We report a COVID-19 patient who experienced bleeding from AVWS in addition to disseminated intravascular coagulation (DIC) during ECMO. The level of high–molecular weight VWF multimers decreased during ECMO therapy, and these findings promptly improved after discontinuation of ECMO. Plasma levels of VWF antigen were extremely high, probably due to endothelial cell damage caused by COVID-19. On the other hand, plasma levels of ADAMTS13 activity were moderately reduced, to 20–30% of normal. The patient was successfully treated with cryoprecipitate in bleeding during ECMO without a reduction in heparin, which might have induced thromboembolism. Bleeding found in this patient might be caused by AVWS and DIC.Severe COVID-19 patients are in a thrombotic state and need to receive anticoagulant therapy. However, once they receive ECMO therapy, bleeding symptoms could be observed. In such cases, physicians should think of AVWS in addition to the side effect of heparin and DIC.     

Anticoagulation in atrial fibrillation: selected controversies including optimal anticoagulation intensity,treatment of intracerebral hemorrhage

Clinical trials during the past 20 years have revolutionized the antithrombotic management of atrial fibrillation. Based on consideration of 30 randomized trials involving 29,017 participants, adjusted-dose warfarin remains the most efficacious prophylaxis against stroke for atrial fibrillation patients at moderate-to-high risk (compared with antiplatelet agents, warfarin reduces stroke by about 40%). The optimal INR for prevention of stroke for most atrial fibrillation patients is probably 2.0–2.5; INRs of 1.6–1.9 provide substantial protection, 80–90% of that afforded by higher intensities. Warfarin-associated intracerebral hemorrhage is an increasing problem as more elderly patients with atrial fibrillation are anticoagulated. Modest reductions in blood pressure results in large decreases in this most dreaded complication of warfarin; anticoagulation of elderly atrial fibrillation patients should be accompanied by a firm commitment to control hypertension. Warfarin-associated intracerebral hemorrhage has a 50% early mortality. A wide range of acute treatments to urgently reverse anticoagulation have been recommended by experts, but prevention is a far better option than treatment of this devastating problem. Disclosure: Dr. Hart chaired the Data Safety Monitoring Boards of the SPORTIF III and V trials and received compensation from Astrazeneca Pharma for this activity; he has had add no affiliation since the trials ended in 2004. He serves on the steering committee, stroke advisory committee and/or data safety monitoring board of several ongoing clinical trials of novel anticoagulants in atrial fibrillation patients.