[Effect of anticoagulant therapy on the course of COVID-19 in comorbid patients].

INTRODUCTION: Analysis of the pathogenesis of coronavirus infection caused SARS-CoV-2 indicates a significant impact of hemorheological disorders on its course and outcomes. It is known that chronic cardiovascular diseases are associated with the risk of severe course and lethal outcomes both in COVID-19 and other infectious diseases. Therefore, in each case it is necessary to study the interaction and mutual influence of different components of the treatment program prescribed to such patients.The purpose of this work was to evaluate the effect of coagulation activity on the course of a novel coronavirus infection (COVID-19) and to justify the management of comorbid patients having been received novel oral anticoagulants (NOACs) in previously selected doses according to indications in concomitant somatic diseases. MATERIAL AND METHODS: Total 76 cases of confirmed coronavirus infection in patients who had been received initial therapy on an outpatient basis were analyzed. 26 patients who received NOACs (rivaroxaban, apixaban, dabigatran) made up the main group and 50 - the comparison (control) group in which patients had not been administered any drugs that affect blood clotting until the episode of COVID-19. All patients have been prescribed therapy following the Provisional guidelines «Prevention, diagnosis and treatment of coronavirus infection (COVID-19)¼ (https://static-0.minzdrav.gov.ru/system/attachments/attaches/). RESULTS AND DISCUSSION: The number of hospitalizations was significantly fewer in the group of patients who had been received NOACs (19 vs. 66% in the control group). No deaths or cases of severe respiratory and/or renal failure were observed in the main group, while adverse outcomes were noted in 14% of patients who had not been administered these drugs. CONCLUSION: Taking NOACs reduces the probability of severe course and adverse outcomes in the development of coronavirus infection caused by SARS-CoV-2, which indicates a significant contribution of coagulation mechanisms to the pathogenesis in COVID-19. There were no indications for drug replacement and correction of anticoagulant therapy regimens in patients who received adequate therapy with oral anticoagulants for treating a non-severe form of coronavirus infection in ambulatory patient settings.

Safety and effectiveness of a prothrombin complex concentrate in approved and off-label indications.

OBJECTIVE: To evaluate the effectiveness and safety of prothrombin complex concentrates (PCCs) in approved and off-label indications. BACKGROUND: PCCs are approved for the urgent reversal of vitamin K antagonists (VKAs). Data concerning the efficacy, safety and dosing for off-label indications are limited, but they are included in massive bleeding protocols. METHODS: This was a retrospective review of cases treated with four-factor PCCs (4F-PCCs) between January 2009 and 2016. Efficacy end-points include: (i) VKA reversal efficacy assessed by international normalised ratio (INR) normalisation (<1·5) and (ii) clinical efficacy as bleeding cessation and/or decreased number of transfused blood components and 24-h mortality in bleeding coagulopathy. The safety end-point is the incidence of thromboembolic events. RESULTS: A total of 328 patients were included (51·8% male, median age 78 years old). Indications were as follows: VKA reversal (66·6%), bleeding coagulopathy (30·5%) and direct anticoagulant (DOAC) reversal due to bleeding (2·5%). VKA reversal was effective in 97·1% of patients, and 76·5% demonstrated complete reversal (INR < 1·5); only 34·3% patients needed hemoderivatives. Prior to emergency procedures, PCCs achieved global responses in 83% of patients, with no bleeding complication during intervention. DOAC reversal was effective in 88·9% of patients. Bleeding cessation was associated with the dose administered (P = 0·002). In coagulopathy bleeding, haemorrhage cessation, established by the International Society of Thrombosis and Haemostais (ISTH) definition, occurred in 56·7% of massive bleeding events and in 42·5% of other coagulopathies; 24-h mortality was 30%, mainly related to active bleeding. Ten thrombotic episodes were observed (3·1%). CONCLUSION: 4F-PCC was effective as adjuvant treatment with an acceptable safety profile, not only for the emergent reversal of VKAs but also for refractory coagulopathy associated with major bleeding.

Disseminated intravascular coagulation after craniotomy.

Disseminated intravascular coagulation (DIC) is reported in neurosurgical patients; however, the incidence of DIC after craniotomy procedures is unknown. Using a surgical database, we identified 3164 patients who underwent primary craniotomy at Mayo Clinic Rochester between January 1, 2000 and December 31, 2004. Potential cases of DIC in this population were identified using 3 search triggers, patients: (1) in whom the diagnosis of DIC was noted on their hospital discharge summary, (2) who received red blood cell-free blood products, or (3) in whom a blood fibrinogen or d-dimer concentration was assessed. Using criteria based on laboratory values, we estimated the incidence of DIC developing within 72 hours of primary craniotomy to be between 13 and 44 per 10,000 patients. Despite a low incidence of DIC, the associated mortality rate was 43% to 75%. Traumatic head injury was a significant risk factor for the development of DIC [odds ratio of trauma was in the range of 16 (95% confidence interval (CI)=5.3-49) to 29 (CI=4.0-204)]. Autologous salvaged blood was administered intraoperatively to 44 patients, and 1 of these developed DIC. Although this small sample of patients receiving salvaged blood requires caution in interpreting the results, the risk of DIC seemed to be greater with salvaged blood than without [odds ratio 24 (CI=2.5-237)]. In children, 2 of 3 patients who developed DIC had congenital malformations of the brain. Findings from this study suggest that DIC is rare after craniotomy, but is often associated with mortality.

Is the "salvaged-cell syndrome" myth or reality?

BACKGROUND: Intraoperative autotransfusion (IAT) has been implicated in anecdotal cases and experimental models to precipitate, aggravate, or exacerbate a coagulopathy. This study assesses this hypothesis. METHODS: A retrospective database review of over 36,000 multispecialty cases of IAT during an 18-year experience was conducted with special reference to the occurrence of coagulopathy (disseminated intravascular coagulation [DIC]) in association with adult respiratory syndrome (ARDS). RESULTS: The incidence of coagulopathy was low (0.05%). A total of 18 cases of DIC/ARDS were identified: 10 associated with ruptured aneurysms, 6 following massive trauma, and 2 after complex redo cardiac surgery. All 18 patients suffered shock and profound hypothermia. The mean transfusion requirement was 28 units. The mortality was 100%. CONCLUSION: Although some degree of bleeding and clotting disorders are not uncommon in major cases, in our experience coagulopathy occurs infrequently and is a result of a complex interaction of shock, hypothermia, and multiple transfusions. It is our contention that these factors trigger the DIC, not the autotransfusor, and that the ARDS results from reperfusion injury following a profound ischemic event, associated in many cases with multiorgan failure.

Protein C and S deficiency in severe infectious purpura of children: a collaborative study of 40 cases.

We studied, in 40 children (mean age: 52 months) with severe infectious purpura, the relationships between protein C (PC) and protein S (PS) levels, and shock, disseminated intravascular coagulation (DIC) and outcome. We determined, on admission, PC antigen (ELISA) and activity (chromogenic test), and total PS (ELISA). Results were expressed as % of normal adult values. Statistical analysis was performed with SAS. Thirty children were in shock, 20 had DIC. All children with DIC, and 10 without DIC were in shock. Of 20 children who were in shock and had DIC, 7 died and 3 had an amputation. PC antigen was significantly decreased in shock children (p less than 0.05), in children with DIC (p less than 0.0005), and in non-survivors (p less than 0.05). PC activity was significantly decreased in shock children (p less than 0.05), in children with DIC (p less than 0.0005), and in non-survivors (p less than 0.005). Total PS was not decreased in shock children, but was significantly decreased in children with DIC (p less than 0.005), and in non-survivors (p less than 0.005). We conclude that PC and PS levels were decreased in our children, and that PC levels were significantly decreased in the presence of shock, DIC, and fatal outcome. PC and antithrombin III (AT III) supplementation, should be evaluated in children with severe infectious purpura with shock and DIC.

Disseminated intravascular coagulation induced by progesterone in the pregnant rat. Prevention by estogens.

Fatal disseminated intravascular coagulation (DIC) was induced in female rats by administration of progesterone in late pregnacy. This prevented parturition, with intrauterine fetal death 2 to 4 days past term and subsequent retention of dead fetuses. Concomitantly with or closely following the intrauterine death of their litters, a large proportion of pregnant rats died with histologically evident DIC. Administration of cortisone, heparin, or disoumarin did not prevent DIC, and xi-aminocaproic acid, acetylsalicylic acid, or an onion-rich diet tended to increase its incidence. Antibiotic regimens gave variable results, with significant decrease in DIC only with a combination of two wide-spectrum penicillins. Neomycin and polymyxin had little effect on susceptible Sprague-dawley derived rats, but polymxin caused a significant increase in DIC in a resistant strain of hooded rats. Fatal maternal DIC was completely prevented only by use of natural or synthetic estrogens concurrently with progesterone, although this did not alter the sequence of abnormally prolonged pregnacy with intrauterine fetal death and retention of dead fetuses. Potencies of estrogens varied greatly, but all compounds tested prevented DIC at adequate dosage levels. Diethylstilbestrol, the most potent drug tested, was completely protective at 1 mug daily given subcutaneously. beta-Estradiol was the most effective natural estrogen, giving complete protection with a 10-mug daily subcutaneous injection. Estrogens were much more potent by subcutaneous injection than by oral ingestion, and toxic side effects were sometimes noted with higher levels of the latter. For estrogen therapy to be effective, it was necessary to begin its use before the expected onset of DIC, and in no instance was there evidence of reversal of this process after signs of illness were observed.

PIP: Fatal disseminated intravascular coagulation (DIC) was induced in female rats by administration of progesterone in late pregnancy. This prevented parturition, with intrauterine fetal death 2-4 days past term and subsequent retention of dead fetuses. Concomitantly with, or closely following the intrauterine death of their litters, a large proportion of pregnant rats died with histologically evident DIC. Administration of cortisone, heparin, or dicoumarin did nothing to prevent DIC, and epsilon-aminocaproic acid, acetylsalicylic acid,or an onion-rich diet tended to increase its incidence. Antibiotic regimens gave variable results, with significant decrease in DIC only with a combination of 2 wide-spectrum penicillins. Neomycin and polymyxin had little effect on susceptible Sprague-Dawley derived rats, but polymyxin caused a significant increase in DIC in a resistant strain of hooded rats. Fatal maternal DIC was completely prevented only by use of natural or synthetic estrogens concurrently with progesterone, although the sequence of abnormally prolonged pregnancy with intrauterine fetal death and retention of dead fetuses remained. Potencies of estrogens varied greatly, but all compounds tested prevented DIC at adequate dosage levels. Diethylstilbestrol, the most potent drug tested, was completely protective at 1 mcg daily given sc. Bate-estradiol was the most effective natural estrogen, giving complete protention with a 10 mcg daily sc injection. Estrogens were much more potent by sc injection than by oral ingestion, and toxic side effects were sometimes noted with higher levels of the latter. For estrogen therapy to be effective, it was necessary to begin its use before the expected onset of DIC. Reversal of this process once DIC has started is beyond the powers of this therapy.