Favorable Outcomes of Anticoagulation With Unfractioned Heparin in Sepsis-Induced Coagulopathy: A Retrospective Analysis of MIMIC-III Database

Backgrounds: Anticoagulation in sepsis-associated disseminated intravascular coagulation (DIC) remains uncertain. The aim of this study was to investigate whether unfractioned heparin (UFH) could improve clinical outcomes in patients with sepsis-induced coagulopathy (SIC).Methods: Septic patients with SIC were identified from the Medical Information Mart for Intensive Care (MIMIC)-III database. Cox-proportional hazards model, logistic regression model and linear regression were used to assess the associations between UFH administration and 28-day mortality, hospital mortality, occurrence of bleeding complications and length of stay, respectively. Propensity score matching (PSM) analysis was used to match the imbalance between patients in the UFH group and the control group. Patients were further stratified according to SIC score and Simplified Acute Physiology Score II (SAPS II).Results: A total of 1,820 septic patients with SIC were included in the data analysis. After PSM, 652 pairs of patients were matched between the patients in the UFH group and the control group. UFH was significantly associated with reduced 28-day mortality (HR, 0.323, 95% CI, 0.258–0.406; p < 0.001) and hospital mortality (HR, 0.380, 95% CI, 0.307–0.472; p < 0.001) without increasing the risks of intracranial hemorrhage (OR, 1.480, 95% CI, 0.955–2.294; p = 0.080) or gastrointestinal bleeding (OR, 1.094, 95% CI, 0.503–2.382; p = 0.820). For subgroup analysis, it didn't change the favorable results of UFH on mortality and UFH didn't increase the risk of hemorrhage in patients with severe disease.Conclusions: The analysis of MIMIC-III database indicated that anticoagulant therapy with UFH may be associated with a survival benefit in patients with SIC.

Low in-hospital mortality rate in patients with COVID-19 receiving thromboprophylaxis: data from the multicentre observational START-COVID Register

COVID-19 infection causes respiratory pathology with severe interstitial pneumonia and extra-pulmonary complications; in particular, it may predispose to thromboembolic disease. The current guidelines recommend the use of thromboprophylaxis in patients with COVID-19, however, the optimal heparin dosage treatment is not well-established. We conducted a multicentre, Italian, retrospective, observational study on COVID-19 patients admitted to ordinary wards, to describe clinical characteristic of patients at admission, bleeding and thrombotic events occurring during hospital stay. The strategies used for thromboprophylaxis and its role on patient outcome were, also, described. 1091 patients hospitalized were included in the START-COVID-19 Register. During hospital stay, 769 (70.7%) patients were treated with antithrombotic drugs: low molecular weight heparin (the great majority enoxaparin), fondaparinux, or unfractioned heparin. These patients were more frequently affected by comorbidities, such as hypertension, atrial fibrillation, previous thromboembolism, neurological disease, and cancer with respect to patients who did not receive thromboprophylaxis. During hospital stay, 1.2% patients had a major bleeding event. All patients were treated with antithrombotic drugs; 5.4%, had venous thromboembolism [30.5% deep vein thrombosis (DVT), 66.1% pulmonary embolism (PE), and 3.4% patients had DVT + PE]. In our cohort the mortality rate was 18.3%. Heparin use was independently associated with survival in patients aged ≥ 59 years at multivariable analysis. We confirmed the high mortality rate of COVID-19 in hospitalized patients in ordinary wards. Treatment with antithrombotic drugs is significantly associated with a reduction of mortality rates especially in patients older than 59 years.

Anticoagulation in Peripheral Artery Disease: Are We There Yet?

Thromboembolism in patients with peripheral artery disease (PAD) represents a common cause of morbidity and mortality. In this article, the authors analyse the use of anticoagulants for patients with PAD. Anticoagulants have been used to reduce the risk of venous thromboembolism, but have recently been applied to the arterial circulation. Heparins were introduced to reduce short-term major adverse limb events in patients undergoing arterial revascularisation. Low molecular weight heparins have allowed easier management and carry a lower risk of bleeding than unfractioned heparin. Vitamin K anticoagulants have been tested in trials that included patients with PAD, showing an increased risk of bleeding when compared with aspirin alone, but longer patency rates for venous surgical bypass, although the evidence remains weak. Those anticoagulants are currently recommended only in patients with PAD who need anticoagulation for other diseases. Direct oral anticoagulants have only recently been investigated for use in patients with PAD. Promising results from low dose rivaroxaban plus aspirin have been recently outlined by a randomised controlled trial and supported by international guidelines.

A “Catastrophic” Heparin-Induced Thrombocytopenia

Background. Heparin-induced thrombocytopenia (HIT) is a transient, antibody-mediated thrombocytopenia syndrome that usually follows exposure to unfractioned heparin (UFH) or low-molecular-weight heparin (LMWH). In contrast to other pathological conditions which lead to thrombocytopenia and bleeding complications, HIT results in a paradoxical prothrombotic state. It is caused by antibodies directed to complexes containing UFH or LMWH and a self-platelet protein: the platelet factor 4 (PF4). The heparin-PF4 immune complex leads to activation of platelets, monocytes, and endothelial cells which release procoagulant proteins and tissue factor with subsequent blood coagulation activation. Case Report. We describe the case of a woman undergone to knee replacement and affected by urosepsis who developed a HIT after exposure to enoxaparin. The thrombotic burden was very impressive involving the arterial and venous cerebral vessel and the venous pulmonary, hepatic, and inferior legs vascular beds. The patient was successfully treated with fondaparinux without recurrent thrombosis or bleeding. The clinical scenario could be named “catastrophic HIT” like the catastrophic antiphospholipid syndrome since they have a similar pathogenetic mechanism involving both platelets and monocytes procoagulant activities and a similar clinical manifestation with a life-threatening multiple arterial and/or venous thromboses. Conclusion. Patients presenting with HIT could show a very impressive thrombotic burden resembling to that of the catastrophic antiphospholipid syndrome. A careful differential diagnosis should be made towards other pathological conditions which lead to thrombocytopenia to avoid an unnecessary and potentially harmful platelet transfusion. Although fondaparinux is off-label, its use in patients with HIT is simple and seems to be effective.

EMBOLI PARU

<p>Emboli paru merupakan salah satu kegawatdaruratan pada bidang kardiovaskular yang cukup sering terjadi dengan berbagai manifestasi klinis dari keadaan yang asimptomatik hingga keadaan yang mengancam nyawa. Insidensi terjadinya emboli paru pada populasi mencapai 23 per 100,000 penduduk dengan tingkat mortalitas mecapai 15%. Emboli paru dapat disebabkan oleh tromboemboli vena, emboli udara, lemak, cairan amnion, fragmen tumor, dan sepsis. Pemeriksaan <em>ventilation-perfusion scintigraphy</em> masih menjadi baku emas untuk menegakkan diagnosis emboli paru. Sedangkan pemeriksaan lain dapat dilakukan untuk membantu klinisi mendiagnosis kejadian emboli paru. Tatalaksana pada emboli paru akut harus dilakukan dengan segera dengan menggunakan antikoagulan seperti unfractioned heparin, LMWH atau vitamin K antagonis, dilanjutkan dengan trombolitik atau embolektomi apabila trombolitik tidak dapat dilakukan. </p>