February 2022: New In Coagulation

by Donna Castellone, MS, MT (ASCP) SH • February 09, 2022

Our Monthly complilation of the latest studies, guidelines and discussions in coagulation.
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The interpretations below are provided by Donna Castellone, MS, MT (ASCP) SH for Aniara Diagnostica.

Managing VTE in Lung Cancer

At the ASCO recent Quality Care Symposium a presentation recommended to use DOACS for the treatment of cancer associated VTE. The National Comprehensive Cancer Network guidelines recommend DOACS to treat cancer as long as they do not have gastric or gastroesophageal lesions.

Patients who had bleeding and VTE were 60 years and older with the medial interval of bleeding with DOACs was 60 days and recurrent VTE was 90 days. The study showed that the outcomes in those with metastatic lung cancer were comparable to results of large randomized trials and is a safe option in this cohort of cancer patients with cancer associated thromboembolism.

There are several scoring systems to help predict the risk of VTE in cancer patients which can range from 1-20%. Risk assessment models include: Khorana score, the Vienna Thrombosis and Cancer score, the Protecht score, the CONKO score, and the COMPASS-CAT model.


Bleeding After Reperfusion Contributes to Cardiac Injury in MI

A new study has shown that damage to the heart after an MI is not only the results of ischemia cause by a blocked artery, but also due to bleeding in the myocardium after the artery has been opened. A new approach is to limit the damage after revascularization that is caused by hemorrhage after reperfusion. This phenomenon is known as reperfusion injury. Hemorrhage could account for up to half of the damage caused by MI, if it can be limited, the size of the infarct could be reduced and translate into better long-term outcomes. This is referred to as an infarct surge and reperfusion injury can contribute to up to 50% of the final infarct size but the factors contributing to the observed variability are unknown.

Microvessels can remain obstructed after reperfusion resulting in intramyocardial hemorrhage. A study of 70 patients with ST-segment elevation MI was conducted to see whether hemorrhage causes expansion of the infarct. Serial cardiac troponin measures were used to assess infarct size. Results showed that patients with intramyocardial hemorrhage had significantly higher cardiac troponin levels post reperfusion and peaked earlier than in patients without hemorrhage.


Standard Anticoagulation May Be Overkill for Pediatric VTE

The small Kids-DOTT trial showed that treating children that had a provoked VTE benefited with a short course of six weeks of anticoagulant therapy versus the standard of 3 months. This provides evidence to support the guideline of using a 6 week course and can be stopped sooner and is as safe as longer treatment. Recurrent VTE and bleeding risks are lower than previously reported in observational studies of children receiving anticoagulation for acute VTE.

The study was a randomized trial conducted from 2008-2021 that included 417 people less than 21 years of age with acute provoked VTE from either a hospitalized event, trauma or central venous catheter. Patients did not present with persistent APA nor complete occlusion on repeat imaging at 6 weeks. They were randomized to receive LMWH either 6 weeks or 3 months with a 2 year follow-up. Median age was 8.3 years and were split between the sexes. Adverse events were most commonly fever reached 26% at 6 weeks and 32% at the 3 month anticoagulant group. Only a small number of children had cancer, or PE were included in the study, so it may not be applicable to these patients. It should not be extrapolated to patients with unprovoked VTE and older patients. Oral anticoagulants were not included in the study.


DOACs Should Be Standard of Care in Cancer-Associated Thrombosis

A meta-analysis showed that cancer patients who had a VTE and were treated with DOACs experienced a 41% decrease in the rate of thrombosis when compared with dalteparin without major bleeding. Data included information from four randomized trials that included almost 2900 patients.

Three DOAC's (edoxaban at 60 mg once a day, rivaroxaban at 15 mg twice daily for 3 weeks followed by 20 mg once a day, and apixaban 10 mg twice a day for 7 days followed by 5 mg twice a day) were compared to dalteparin was given at a dose of 200 IU/kg daily for 1 month followed by 150 IU/kg daily thereafter. Outcomes were measured to include VTE recurrence, major bleeding and clinically relevant nonmajor bleeding.

There were 5.6% VTE recurrent events in the DOAC group and 9.1% in the dalteparin, with major bleeding of 4.8% in the DOAC and 3.6% in the dalteparin, but not considered statistically significant. However clinically relevant nonmajor bleeding events was significantly higher for those with DOAC vs dalteparin.

Individually, rivaroxaban reduced VTE by 59% and apixaban by 42% when compared to daltiparin. Edoxaban increased the risk of major bleeding compared with dalteparin and rivaroxaban significantly increased the risk of clinically relevant nonmajor bleeding. The subanalysis shows that apixaban may have an edge over three other DOACs since it did not increase the risk of major bleeding and clinically relevant nonmajor bleeding.


Does Omicron Pose as Much of a Blood Clot Threat?

The initial wave of COVID-19 resulted complications in blood clots including pulmonary embolism, clots in dialysis lines and emergent strokes. With the Omicron variant as the prevalent strain there appears to be a decrease in clotting complications. Since this variant causes less severe disease, it may carry a lower risk of clots.

In the initial waves of the pandemic it was reported that 16.5% of COVID patients presented with a PE and 14.8% presented with a DVT with those in the ICU having a higher risk up to 21% versus 9% who were just hospitalized. Most critical care patients appear to be at the highest risk of clotting. Clotting may also be diminished due to the widespread use of anticoagulation therapy among at risk patients.

The previous strains of SARS-CoV-2 cause an inflammatory response that also increased the risk of blood clots. This type of response is not seen with Omicron. Also, the PE that occurred during the first and second waves were in situ lung clots rather than clots that broke off and traveled to the lungs, while Omicron shows evidence of being limited to the upper respiratory airway being less likely to cause clots directly in the lungs.

Patients with increased risk factors still need to be watched for an increased risk of blood clots. Those risks include advanced age, history of CPD, history of cancer, immobility, history of sepsis, or infection. Those patients with extremely elevated D-dimer levels should be closely monitored due to an increased risk of thrombosis and death.


Measuring Direct Oral Anticoagulants- when, how

Laboratories don't have to measure DOACs, but may want to measure levels in some situations. The drugs, dabigatran, rivaroxaban, apixaban and edoxaban have had peak and trough ranges evaluated in clinical trials for DVT and PE. The ICSH will update its recommendations from 2021 on DOACs measurements to help determine if a patient is sufficiently anticoagulated. There is a yearly risk of 1-2% for major bleeding and 1-2% risk of VTE with DOACs and several studies have demonstrated a dose response relationship between DOAC concentrations and adverse events. High trough levels correspond to a higher risk of bleeding while lowest trough levels correlate with thromboembolic events. Patients could benefit from tailored DOAC therapy in particular those with high or low body weight, impaired kidney function, or those who restart anticoagulation after a major bleed.

The possible indications for testing DOAC in non-urgent situations are advanced ae, severe renal failure, high bleeding risk, BMI above 40 kg/m. Urgent situations include acute bleeding and where reversal of DOAC is required.

It has been demonstrated that there is significant variability and the impact of these drugs on the PT, aPTT and thrombin time and they may not be reliable to detect the presence of on-therapy concentration of all DOACs and should not be used to quantify DOAC concentration. Recommendations state that in life threatening conditions tests for quantifying DOACs should be performed to manage the patient. A normal thrombin time will exclude the presence of dabigatran concentration.

Viscoelastic assays are also not sensitive to DOAC effects. On site assays to quantitate levels could be performed by LC/MS or by performing an anti-Xa assay using a DOAC specific calibrator. There are a limited number of FDA approved calibrator material.




Antithrombotic Therapy for Stroke Prevention in Patients With Ischemic Stroke With Aspirin Treatment Failure

Jay B. Lusk, BSc; Haolin Xu, MS; Eric D. Peterson, MD, MPH; Deepak L. Bhatt, MD, MPH; Gregg C. Fonarow, MD; Eric E. Smith, MD, MPH; Roland Matsouaka, PhD; Lee H. Schwamm, MD; Ying Xian, MD, PhD

Stroke. 2021;52(12):e777-e781.



Background and Purpose: Many older patients presenting with acute ischemic stroke were already taking aspirin before admission. However, the management strategy for patients with aspirin treatment failure has not been fully established.

Methods: We used data from the American Heart Association Get With The Guidelines Stroke Registry to describe discharge antithrombotic treatment patterns among Medicare beneficiaries with ischemic stroke who were taking aspirin before their stroke and were discharged alive from 1734 hospitals in the United States between October 2012 and December 2017.

Results: Of 261 634 ischemic stroke survivors, 100 016 (38.2%) were taking aspirin monotherapy before stroke. Among them, 44.4% of patients remained on aspirin monotherapy at discharge (20.9% 81 mg, 18.2% 325 mg, 5.3% other or unknown dose). The next most common therapy choice was dual antiplatelet therapy (24.6%), followed by clopidogrel monotherapy (17.8%). The remaining 13.2% of patients were discharged on either aspirin/dipyridamole, warfarin, or nonvitamin K antagonist oral anticoagulants with or without antiplatelet, or no antithrombotic therapy at all.

Conclusions: Nearly half of patients with ischemic stroke while on preventive therapy with aspirin are discharged on aspirin monotherapy without changing antithrombotic class, while the other half are discharged on clopidogrel monotherapy, dual antiplatelet therapy, or other less common agents. These findings emphasize the need for future research to identify best management strategies for this very common and complex clinical scenario.


Rate of venous thromboembolism in gynecologic patients on an ERAS pathway

Journal of Clinical Oncology 39, no. 28_suppl

Jolyn Sharpe Taylor, Maria Iniesta-Donate, Katherine Cain, Javier Lasala, Gabriel Mena, Andres S. Zorilla Vaca,


Background: Venous thromboembolism (VTE) is a serious and potentially life-threatening complication of surgery. An Enhanced Recovery After Surgery (ERAS) program is a multimodal care pathway meant to facilitate faster recovery from surgery. ERAS protocols include mechanical and pharmacologic VTE prophylaxis and rapid return to ambulation. Our objective was to evaluate the rate of symptomatic VTE on an ERAS pathway among patients undergoing open and minimally invasive gynecologic surgery (MIS).

Methods: Data was collected prospectively on patients undergoing gynecologic surgery on the ERAS pathway at a single academic institution between November 1, 2014 and March 31, 2021. For patients undergoing MIS data were collected from February 1, 2016 to March 31, 2021. Patients undergoing emergency surgery or requiring therapeutic anticoagulation prior to surgery were excluded. For planned open surgery, patients received heparin prophylaxis prior to surgery, sequential compression device (SCD) during surgery and goal directed fluid management. If also diagnosed with malignancy, patients received extended VTE prophylaxis with low molecular weight heparin for 28 days after surgery starting postoperative day 1. For planned MIS, patients received SCD and goal directed fluid management. Descriptive statistics, univariate and multivariate statistical analyses were performed.

Results: Of the 3,932 patients, 2,016 (51%) underwent laparotomy, 1,541 (39%) laparoscopy and 375 (10%) robotic approach. The incidence of thromboembolism was 0.5% (N = 21) overall, 0.8% (N = 17) with open approach and 0.2% (N = 4) with MIS approach. Among laparotomy patients, there was 88% compliance with preoperative heparin prophylaxis. Characteristics associated with developing a VTE were black race, malignancy, open surgical approach, surgical time, surgical complexity, and receipt of intraoperative blood transfusion. On multivariate analysis, black race and transfusion remained associated with VTE. Among laparotomy patients, the rate of intraoperative blood transfusion was 5.9% (N = 120), reoperation for bleeding 0.3% (N = 5) and reoperation for hematoma 0.2% (N = 3).

Conclusions: We found a low rate of VTE among patients undergoing laparotomy and MIS under an ERAS pathway. The rate of VTE following MIS surgery was low without use of extended pharmacologic VTE prophylaxis or receipt of preoperative prophylactic heparin. Receipt of preoperative heparin prophylaxis prior to open surgery is safe with a low complication rate. This establishes a benchmark for the expected rate of VTE following gynecologic surgery on an ERAS pathway.


A Review of Venous Thromboembolism Risk Assessment and Prophylaxis in Plastic Surgery

Nikhil A. Agrawal, M.D.; Kirsty Hillier, M.D.; Riten Kumar, M.D., M.Sc.; Shayan A. Izaddoost, M.D., Ph.D.; Rod J. Rohrich, M.D.

Plast Reconstr Surg. 2022;149(1):121e-129e.



Background: Venous thromboembolism is a significant cause of postoperative death and morbidity. While prophylactic and treatment regimens exist, they usually come with some risk of clinically relevant bleeding and, thus, must be considered carefully for each individual patient.

Methods: This special topic article represents a review of current evidence regarding venous thromboembolism risk, biology, and prevention in plastic surgery patients. The specific types and duration of available prophylaxis are also reviewed. The balance of venous thromboembolism risk must be weighed against the risk of hemorrhage.

Results: Though alternatives exist, the most validated risk assessment tool is the 2005 modification of the Caprini Risk Assessment Model. Controversies remain regarding recommendations for outpatient and low risk cosmetic patients. The authors additionally make recommendations for high-risk patients regarding the use of tranexamic acid, estrogen therapy, anesthesia, and prophylaxis regimens.

Conclusion: Our profession has made great strides in understanding the science behind venous thromboembolism, risk stratification for patients, and prophylactic regimens; yet, continued studies and definitive data are needed.