Occam’s Razor and Managing Acute Thrombosis in the COVID-19 Era

The COVID-19 pandemic has profoundly influenced the practice of medicine in Australia over the last 24 months. Recently, the development of several vaccines to COVID-19 has been accompanied by reports of an associated rare syndrome of thrombosis and thrombocytopaenia (VITTS). The possibility of this rare disorder confronts all clinicians who deal with acute thrombosis, particularly given the prevalence of patients who have recently been immunised. However, VITTS remains rare, and we believe unnecessary focus on its potential diagnosis may distract from other more common causes of acute thrombosis. We discuss this with reference to a recent case at our institution.

Acute Portal and Superior Mesenteric Vein Thrombosis with Topical Testosterone Therapy: An Adverse Drug Event Case Report

This is a case report of a 55-year-old Caucasian male prescribed topical testosterone therapy for 12 months prior to admission, when he was diagnosed with acute thrombosis in the portal vein (PVT) and superior mesenteric vein (SMV). The patient had a negative thrombophilia workup, including Factor V Leiden, Prothrombin G20210A, and JAK2 V617F mutations. There were no other pertinent laboratory markers that raised concern for the cause of thrombus. No strong familial history of venous thromboembolism (VTE) was reported during the patient’s initial workup. With this in mind, the patient’s use of topical testosterone therapy was considered the most likely risk factor for the PVT and SMV thrombus. During hospitalization, the patient was initiated on therapeutic anticoagulation with a heparin drip and discharged to home on apixaban for 3 months with extended therapy to be determined by outpatient hematologist. With no other identified VTE risk factors, probability that this patient’s VTE was attributed to testosterone was evaluated using the Naranjo scale with a calculated score of 6, which classifies the adverse reaction as “likely.” Clinicians should be aware of the possibility that topical testosterone therapy may be a risk factor for venous thrombosis in unusual sites.

A Case of Extensive Splanchnic Vein Thrombosis in a COVID-19 Patient and a Review of the Literature

: Splanchnic vein thrombosis is one of the rare complications of coronavirus disease 2019 (COVID-19). A 43-year-old woman presented with splanchnic vein thrombosis as a rare extrapulmonary complication of COVID-19. She was previously healthy without a medical history of coagulopathy before hospital admission. She complained of epigastric pain, along with nausea and vomiting. Enhanced abdominopelvic CT scan demonstrated extensive acute thrombosis in the portal, superior mesenteric, and splenic veins with total occlusion. Intestinal ischemia or infarction was not clinically observed. All thrombophilia screening tests yielded negative results. Under anticoagulation therapy, she recovered dramatically and was discharged from the hospital. Imaging findings can be used to confirm splanchnic vein thrombosis when a COVID-19 patient has abdominal symptoms.

High Risk of Venous Thrombosis Recurrence in Fully Anticoagulated Patient with Antithrombin Deficiency during COVID-19: A Case Report

Coagulation dysfunction is a serious issue in patients with Coronavirus disease-19 (COVID-19). With regard to recently published studies, a high number of patients with acute respiratory distress syndrome (ARDS) secondary to COVID-19 developed life-threatening thrombotic complications despite anticoagulation. We report a case of young woman with the type-II heparin-binding site (HBS) antithrombin (AT) deficiency (Budapest 3-homozygous), who developed acute deep vein thrombosis on two occasions due to COVID-19 infection in the course of stable anticoagulation with vitamin K antagonist. The first thrombotic event was observed during mild COVID-19 infection, while the second thrombotic event she developed 2 months after she was negative for severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2). Our case highlights the complexity of the treatment in this particular type of thrombophilia and the need for precaution even in mild forms of viral infection. In the treatment of acute thrombosis, AT-deficient patients may benefit from the use of AT concentrate along with low-molecular weight heparin (LMWH), while in cases of type II-HBS, AT supplementation is mandatory.

Additional risk factors for in-hospital ischemic stroke. Hypercoagulation syndrome

The risk of ischemic stroke in inpatients is higher than in the general population. This is due to both the greater comorbidity of inpatients and the presence of additional risk factors, the most studied of which are iatrogenic interventions. At the same time, the higher the probability of developing an ischemic stroke, the more risk factors the patient has. An important link in the pathogenesis of in-hospital ischemic stroke is the activation of the hemostasis system, which is an obligate consequence of a typical pathological process underlying diseases and injuries that led to hospitalization: blood loss, inflammation, mechanical tissue damage, dehydration, etc. In foreign literature, this condition is attributed to the group of acquired thrombophilia, in domestic literature the term hypercoagulation syndrome has become more widespread. Iatrogenic effects can also play an important role in the pathogenesis of hypercoagulation syndrome. It is characterized by increased readiness for thrombosis, clinical and laboratory signs of hypercoagulation, activation of various factors and components of coagulation, decreased fibrinolysis, but without the development of acute thrombosis. Hypercoagulation syndrome is rarely assessed in routine practice as a risk factor for ischemic stroke, however, it can act as an additional and main risk factor for the development of all subtypes of ischemic stroke (according to the TOAST classification), including the ESUS concept. In this regard, it is advisable to distinguish in its structure: chronic (existing before hospitalization: hereditary and/or acquired) and acute (situational, developed as a result of the underlying disease, its complications or iatrogenic effects) hypercoagulation syndromes. To designate a group of acute pathological conditions predisposing to the development of hypercoagulation syndrome, systemic and/or local thrombotic complications, including in-hospital ischemic stroke, and requiring increased preventive measures, it seems pathogenetically justified, understandable and convenient to use the term situational hypercoagulation conditions (1 table, bibliography: 19 refs)

432 ACS-STEMI in a young man with triple positive antiphospholipid syndrome: clinical implications about antithrombotic therapy management

Antiphospholipid antibody syndrome (APS) is a systemic autoimmune disorder characterized by venous and arterial thromboembolic (TE) disease, and/or pregnancy morbidity, associated with persistent elevated antiphospholipid antibodies (lupus anticoagulant, LA, anticardiolipin, aCL, and anti-beta2-glycoprotein I, anti-β2GPI). A 51 year-old man, smoker, presented to our ER with chest pain. EKG showed Q waves and STE in the anterior leads, with increased troponin levels. A diagnosis of anterior STEMI was made and he was taken into our catheterization laboratory, where a high burden thrombotic plaque determining LM and ostial LAD subocclusion was treated with PPCI and a DES implantation; in addition, multiple failed PCI attempts were performed on a distal LAD occlusion, and an integrilin bolus was administered. The patient was admitted to our CICU and a DAPT with ASA and Ticagrelor was started. TTE showed LVEF 40%, apical akinesis, septal and anterior hypokinesis, and no significant valve disease. An aPTT abnormal value (100.5 s; reference range 25–38.5 s) was detected, not corrected by aPTT mixing study. Given suspected autoimmune prothrombotic state, normal Hb and PLT values and low bleeding risk, LMWH 100 IU/kg every 12 h was started, in addition to DAPT with switch from Ticagrelor to Clopidogrel. LA and aCL and anti-β2GPI IgG were positive, with negativity of others rheumatologic tests, confirming primary APS diagnosis. Repeat TTE showed EF 50%. The patient was discharged in ‘triple therapy’ (DAPT plus LMWH), and referred to the rheumatology clinic. LA, aCL, and anti-β2GPI tests 12 weeks later were positive, confirming a triple positive APS and satisfying revised Sapporo criteria. The rheumatologist switched therapy to Clopidogrel plus Warfarin. At 3 months follow-up, the patient, former smoker, was asymptomatic and TTE confirmed EF 50%, so he was recommended to continue with his medical therapy. APS is rarely associated with AMI (∼5.5%) and in only 2.8% cases AMI represents the onset of the disease. AMI pathogenesis in APS is considered to be acute thrombosis of coronary arteries, in contrast with atherosclerotic plaque rupture in typical AMI. Key discriminators to identify APS as potential underlying cause of AMI include young age, previous unprovoked thromboses, low platelets count (they are consumed in the thrombotic process), high aPTT value (LA may interfere with assembly of the prothrombinase complex on phospholipids), coronary artery thromboses in the setting of otherwise normal otherwise appearing coronary arteries. APS antibodies have also pro-inflammatory activity on vascular endothelial cells, leading to accelerated atherosclerosis. aGAPSS score (high risk ≥10) is useful for risk stratification of recurrent thrombosis and AMI in young patients with APS. The treatment of AMI in APS is therefore a clinical challenge. Strict management of additional CV risk factors is crucial. VKA (INR >3 with Warfarin, INR2–3 with Warfarin and ASA) should be provided for life, because of the very high risk of recurrent TE. DOACs are less effective and less safe than VKAs for TE prevention in APS. The role of coronary stents, considering higher rates of stent thrombosis after PCI in APS patients triple therapy concomitant risks, requires further studies. Due to lack of large, randomized, prospective studies, there is no clear experts consensus about optimal antithrombotic therapy in secondary prevention after arterial TE. APS patients with STEMI should undergo PCI, usually associated with thrombus aspiration, and in selected cases DES implantation in culprit lesion followed by triple antithrombotic therapy with short-term DAPT and long-term VKA.

The P2Y12 Receptor Antagonist Selatogrel Dissolves Preformed Platelet Thrombi In Vivo

Selatogrel, a potent and reversible antagonist of the P2Y12 receptor, inhibited FeCl3-induced thrombosis in rats. Here, we report the anti-thrombotic effect of selatogrel after subcutaneous applications in guinea pigs and mice. Selatogrel inhibited platelet function only 10 min after subcutaneous application in mice. In addition, in a modified Folts thrombosis model in guinea pigs, selatogrel prevented a decrease in blood-flow, indicative of the inhibition of ongoing thrombosis, approximately 10 min after subcutaneous injection. Selatogrel fully normalised blood flow; therefore, we speculate that it may not only prevent, but also dissolve, platelet thrombi. Thrombus dissolution was investigated using real-time intravital microscopy in mice. The infusion of selatogrel during ongoing platelet thrombus formation stopped growth and induced the dissolution of the preformed platelet thrombus. In addition, platelet-rich thrombi were given 30 min to consolidate in vivo. The infusion of selatogrel dissolved the preformed and consolidated platelet thrombi. Dissolution was limited to the disintegration of the occluding part of the platelet thrombi, leaving small mural platelet aggregates to seal the blood vessel. Therefore, our experiments uncovered a novel advantage of selatogrel: the dissolution of pre-formed thrombi without the disintegration of haemostatic seals, suggesting a bipartite benefit of the early application of selatogrel in patients with acute thrombosis.

SURGICAL TREATMENT OF ACUTE THROMBOSIS ARTERIES OF INFRAPOPLITEAL SEGMENT

Aim of the study. Aim of the study was to analyze the outcomes of surgical treatment of acute thrombosis of the popliteal-tibial segment arteries with various etiological factors of its occurrence. The analysis of the surgical treatment of 40 patients with acute thrombosis of the popliteal-tibial segment arteries was carried out for the period from 2014 to 2020. Depending on the pathogenesis of acute thrombosis of the popliteal-tibial segment arteries, the patients were divided into three groups: Group 1 – 17 (42.5%) patients with acute arterial thrombosis of the popliteal-tibial segment caused by embolism or thrombosis in the background of stenotic-occlusive diseases of the lower extremitiesvessels; Group 2 – 15 (37.5%) patients with acute arterial thrombosis of the popliteal-tibial segment in the background of thromboangiitisobliterans of the lower extremities (Buerger's disease); Group 3 – 8 (20%) patients with acute arterial thrombosis of the popliteal-tibial segment in the background of popliteal artery aneurysm. During the follow-up period of 2 months, the incidence of rethrombosis and amputation of the lower limb in the patients of Group A was 5.9% and 5.9%, respectively. In Group B, the incidence of rethrombosis and amputation of the lower limb was 73.3% and 40.0%, respectively. In group C, the incidence of rethrombosis and amputation of the lower limb was 12.5% and 12.5%, respectively. Conclusions. In patients with acute arterial thrombosis of the popliteal-tibial segment in the background of embolism or stenotic-occlusive diseases, combined endovascular or hybrid surgical interventions showed better results compared to open thrombectomy, in which rethrombosis was diagnosed in 14.3% of cases. In patients with thromboangiitis obliterans of the lower extremities, regional catheter-directed thrombolysis showed better (p=0,04) results compared to open thrombectomy and endovascular interventions, in which rethrombosis was diagnosed in 90% and 100% of cases, respectively. In patients with popliteal artery aneurysm, open surgical interventions or regional catheter-directed thrombolysis showed better results compared to endovascular interventions, in which rethrombosis was diagnosed in 50% of cases.