Anti Xa activity after high dose LMWH thrombosis prophylaxis in covid 19 patients at the intensive care unit.

INTRODUCTION: Coagulopathy in Coronavirus disease 2019 (covid-19) has been demonstrated by an increase in D-dimer, prothrombin time (PT), fibrinogen and factor VIII. Venous thromboembolic events are a common abnormality in patients with covid-19. We evaluate the results of intensive care unit (ICU) thrombosis prophylaxis of 5700 international unit (IU) nadroparin low molecular weight heparin (LMWH) twice daily. METHODS: After introduction of this high-dose pharmacological thrombosis prophylaxis twice weekly anti-factor Xa (anti Xa) concentrations and results from routine laboratory and viscoelastic hemostatic tests in 16 ICU covid-19 patients were evaluated. RESULTS: During one week, median peak anti Xa activities were 0.38 [0.16-0.45] and 0.38 [0.20-0.58] at time point 1 and 2 respectively. Laboratory coagulation tests showed PT, AT and platelet count (PltC) values within normal range and markedly increased D-dimer and fibrinogen levels. Viscoelastic tests showed a maximum clot strength just above normal reference value, while fibrin clot strength was strongly increased. The overall contribution of fibrin to clot strength was high with 71 [56-85]%. CONCLUSION: Anti Xa activity was within the target range of pharmacodynamic endpoint for covid-19 patients but viscoelastic tests still demonstrated a procoagulant pattern.

The influence of aspirin dose and glycemic control on platelet inhibition in patients with type 2 diabetes mellitus.

BACKGROUND: Low-dose aspirin seems to offer no benefit in the primary prevention of cardiovascular disease in type 2 diabetes mellitus (DM2). The anti-platelet effect may be diminished by poor glycemic control or inadequate dosing of aspirin. OBJECTIVES: To study the effects of both glycemic control and increasing aspirin dose on platelet response to aspirin in DM2 patients and matched controls. PATIENTS/METHODS: Platelet effects of increasing doses of aspirin (30, 100 and 300 mg daily) were prospectively assessed in 94 DM2 patients and 25 matched controls by measuring thromboxane levels in urine (11-dhTxB2) and platelet aggregation using VerifyNow(®) and light transmission aggregometry (LTA). DM2 patients were stratified for glycemic control (hemoglobin-A1c [HbA1c] ≤ 53, 53-69, ≥ 69 mmol mol(-1)). RESULTS: At baseline, median 11-dhTxB2 excretion was higher in the poorly controlled patients (77 ng mmol(-1)), and the moderately controlled (84 ng mmol(-1)) compared with the well-controlled patients (64 ng mmol(-1)) and controls (53 ng mmol(-1)), P < 0.01. Next, 30 mg of aspirin reduced 11-dhTxB2 excretion to 31, 29 and 24 ng mmol(-1) in the poorly, moderately and well-controlled patients, respectively, and to 19 ng mmol(-1) in controls, P < 0.001. VerifyNow(®) and LTA were also incompletely suppressed in DM2 patients using 30 mg of aspirin, but 100 mg resulted in similar platelet suppression in all groups, with no additional effect of 300 mg. CONCLUSIONS: DM2 patients with inadequate glycemic control (HbA1c > 53 mmol mol(-1)) have higher baseline platelet activity and incomplete suppression of platelet activity with 30 mg of aspirin. However, 100 mg of aspirin leads to optimal inhibition irrespective of glycemic control, and 300 mg does not further improve platelet suppression.

Effect of the selective serotonin reuptake inhibitor paroxetine on platelet function is modified by a SLC6A4 serotonin transporter polymorphism.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) have been associated with an increased bleeding tendency. OBJECTIVES: To prospectively quantify the dose-response effects of paroxetine and the influence of the serotonin transporter gene (SLC6A4) promoter polymorphism (5-HTTLPR) on platelet function. METHODS: Nineteen drug-free psychiatric outpatients (44.5 +/- 10.8 years) were tested before and after 6 weeks of paroxetine treatment (20 mg day(-1)). Based on clinical symptoms, paroxetine dosages were increased (40-50 mg day(-1)) for 6 more weeks in 11 patients. Parameters related to platelet function were assessed by bleeding time, platelet function analyzer (PFA), platelet serotonin, platelet factor 4 (PF4), beta-thromboglobulin (beta-TG), and aggregation tests. RESULTS: Paroxetine 20 mg day(-1) increased mean bleeding time by 1.2 min (95% confidence interval (95% CI) -0.2-2.7) and reduced median platelet serotonin level (463 ng 10(-9) platelets; inter quartile range (IQR) 361-666), and platelet ss-TG concentration (3.1 IU 10(-6) platelets; IQR 0.3-6.0). Other platelet parameters did not change significantly. Serial platelet aggregation tests did not become abnormal. Paroxetine dose-escalation did not further influence platelet function. However, 5-HTTLPR polymorphisms modified these effects: in L(A)/L(A)-carriers, bleeding times did not change (-0.2 min; 95% CI -0.6 to 0.9), while bleeding times significantly increased in <2L(A)-allele carriers (2.3 min; 95% CI 0.5 to 4.07; P = 0.032). Platelet serotonin decreases were larger in patients without L(A)-alleles (868 ng 10(-9) platelets; IQR 585 to 1213) than in > or =1 L(A)-allele carriers (457 ng 10(-9) platelets; IQR 392 to 598; P = 0.035). PFA closure time and PF4 increased significantly in patients without L(A)-alleles. CONCLUSIONS: Paroxetine 20 mg day(-1) does not increase overall bleeding time, but impairs platelet function by decreasing the levels of platelet serotonin and platelet ss-TG. These paroxetine effects appear to be mediated by 5-HTTLPR, with most pronounced effects in patients without L(A)-alleles.

Catastrophic antiphospholipid syndrome mimicking a malignant pancreatic tumour--a case report.

The catastrophic antiphospholipid syndrome is characterised by rapid onset thromboses, often resistant to conventional anticoagulant treatment, and resulting in life threatening multiple organ dysfunction. The diagnosis of catastrophic antiphospholipid syndrome may be difficult, predominantly due to its frequently atypical presentation. We report a case of a 35-year-old female who presented with a pancreatic tumour and extensive thromboses. Following a storm of ischemic events due to thrombotic occlusions in spite of therapeutic heparin dose, the suspicion of catastrophic antiphospholipid syndrome emerged. The patient was successfully treated with anticoagulants, immunoglobulins, plasmapheresis and rituximab. The present report shows that the use of the diluted Russell's viper venom time can be helpful in providing additional information on the lupus anticoagulants antibody status, allowing careful monitoring of lupus anticoagulants conversion and hence response to therapy.

Pediatric venous thromboembolic disease in one single center: congenital prothrombotic disorders and the clinical outcome.

To learn more about the frequencies of congenital prothrombotic disorders in pediatric venous thromboembolism (VTE) and the outcome of this disease, we evaluated consecutive patients from 0 to 18 years with objectively diagnosed VTE at a single tertiary center over a 12-year period. We included 100 patients, with a median age at diagnosis of 1.0 year (range 2 days to 17 years). At least one underlying clinical condition was present in 96% of the patients. Factor (F)V G1691A mutation was present in 13%, FII G20210A mutation in 3%, antithrombin deficiency in 1%, protein C deficiency in 1% and protein S deficiency in 1% of the tested patients. Combined defects were present in 2.6% of the 77 patients with a complete work-up. Positive family history appeared to be the only predictor for positive testing for congenital disorders (OR 14.9, 95% CI 1.9-113). The overall mortality rate was 20%. The cumulative recurrence-free survival was 92% after 1 year of follow-up, and 82% after 7 years. The incidence and severity of the post-thrombotic syndrome was analyzed in a subgroup of 33 patients with VTE of the lower extremities. Twenty-three (70%) patients developed PTS: moderate in three and mild in 20 patients. In conclusion, congenital prothrombotic disorders seem to play a role in the development of pediatric VTE, and the risk of complications of this disease is high.