Anesthesia strategy for factor X deficiency coagulopathy: case report

Abstract Factor X deficiency ranks among the rarest coagulopathies and has a variable presentation spectrum. We intend to present a proposal for anesthesia protocol for individuals with the coagulopathy. The excision of an ovarian neoplasm was proposed for a 26-year-old, female, ASA II patient, with congenital Factor X deficiency. Physical examination and lab tests were normal, except for Prothrombin Time (PT) 22.1s (VR: 8-14s), International Normalized Ratio (INR) 1.99 (VR: 0.8-1.2) and Activated Partial Thromboplastin Time (aPTT) 41.4s (VR: 25-37s). We concluded that a history of bleeding should always be investigated, along with a pre-anesthetic coagulation study.

COVID19 coagulopathy in Caucasian patients.

Although the pathophysiology underlying severe COVID19 remains poorly understood, accumulating data suggest that a lung-centric coagulopathy may play an important role. Elevated D-dimer levels which correlated inversely with overall survival were recently reported in Chinese cohort studies. Critically however, ethnicity has major effects on thrombotic risk, with a 3-4-fold lower risk in Chinese compared to Caucasians and a significantly higher risk in African-Americans. In this study, we investigated COVID19 coagulopathy in Caucasian patients. Our findings confirm that severe COVID19 infection is associated with a significant coagulopathy that correlates with disease severity. Importantly however, Caucasian COVID19 patients on low molecular weight heparin thromboprophylaxis rarely develop overt disseminated intravascular coagulation (DIC). In rare COVID19 cases where DIC does develop, it tends to be restricted to late-stage disease. Collectively, these data suggest that the diffuse bilateral pulmonary inflammation observed in COVID19 is associated with a novel pulmonary-specific vasculopathy termed pulmonary intravascular coagulopathy (PIC) as distinct to DIC. Given that thrombotic risk is significantly impacted by race, coupled with the accumulating evidence that coagulopathy is important in COVID19 pathogenesis, our findings raise the intriguing possibility that pulmonary vasculopathy may contribute to the unexplained differences that are beginning to emerge highlighting racial susceptibility to COVID19 mortality.

Anticoagulant proteins in a population of Mexican mestizo donors.

BACKGROUND: To determine the activity of antithrombin (AT), protein C (PC), and protein S (PS), as well as the frequency of deficiencies of these proteins in a population of healthy Mexican mestizo blood donors. METHODS: AT, PC, and PS were determined from 1,502 plasma samples of healthy blood donors by using commercial kits in a coagulometer 4 STA (Diagnostica Stago, Asnières, France). RESULTS: A total of 741 women and 761 men were under study. They were divided into age range groups (18-24, 25-34, 35-44, 45-54, and 55-64 years). Activity of AT, PC, and PS was determined. For AT, activity values were specific for each age group according to gender when it had to do with PS, as well as when PC was determined. Frequencies of AT, PC, PS, and activated PC resistance activity deficiencies were obtained from reference levels (RLs) and average levels of this study. Differences were found between both frequencies for AT, PC, and PS, and the average levels obtained were used in this study. The frequencies of the activity deficiencies obtained through the values gotten in this population were: AT, 0.6%; PC, 1.06% (which is higher than the one obtained using the RLs described by commercial kits 0.33% and 0.66%, respectively); and PS, 1% (which is less than 4.5%). CONCLUSIONS: It is necessary to know the characteristics and biological behavior of the coagulation proteins in the Mexican population because the RLs used have been established for populations that are genetically different.

Thrombophilic gene polymorphisms in puerperal cerebral veno-sinus thrombosis.

Puerperal cerebral veno-sinus thrombosis (PCVT) is a common form of stroke in young women in India, which is associated with high morbidity and mortality. The frequency of PCVT in India is 10 to 12 times more compared to western population. As yet, the etiology of this condition is unclear. Our aim was to study the prevalence and the role of the common genetic polymorphisms associated with thrombophilia such as factor V Leiden, prothrombin G20210A and methylene tetrahydrofolate reductase (MTHFR) C677T, in aseptic PCVT. We investigated 86 women with PCVT and 86 age-matched women with no post-partum complications. Polymerase chain reaction (PCR)/restriction fragment length polymorphism analysis was used to identify their genotypes. The frequency of the three polymorphisms in cases and controls were: factor V Leiden, 2.3% versus 1.2% (OR 0.49, 95% CI=0.02-7.12, p=1.000) and MTHFR C677T, 16.3% versus 17.4% (OR 0.92, 95% CI=0.39-2.19, p=0.838). The prothrombin G20210A variant was not detected in either patients or controls. The clinical characteristics of the PCVT patients with the polymorphisms did not differ significantly from those without them. In our series of PCVT patients, the risk associated with the established thrombophilic risk factors is insignificant. Exploration of these gene polymorphisms seems to be of limited value in the investigation of PCVT in south Indian women.

Impaired fibrinolysis and increased fibrinogen levels in South Asian subjects.

The potential role of haemostatic risk markers is largely unexplored in South Asians, who have increased morbidity and mortality from cardiovascular disease and an increased prevalence of insulin resistance. To investigate differences in thrombotic risk markers between South Asian and White populations, 42 Asian and 50 White males and 96 Asian and 80 White females, clinically free from vascular disease, were recruited. Venous blood samples were taken for measures of haemostasis and determination of blood lipids. South Asian females showed lower fasting blood glucose than White females (4.6 vs. 4.8 mmol/l, P<0.008). In the South Asian population, total cholesterol was lower in females, with a similar trend in males (females 5.0 vs. 5.5 mmol/l, P<0.001; males 5.1 vs. WM 5.5 mmol/l, P=0.09), but no difference in triglyceride levels. South Asian subjects of both genders had markedly higher levels of fibrinogen (females 3.3 vs. 2.8 mg/dl, P<0.0005; males 3.0 vs. 2.5 mg/dl P<0.002) and PAI-1 activity (females 14.6 vs. 8.7 ng/ml, P<0.0005, males 21.3 vs. 12.2 ng/ml, ) P<0.0005). Factor VII:C was lower in both South Asian groups (females 110.9 vs. 122.4%, P<0.005; males 103.3 vs. 125%, P<0.0005). Factor XII was lower in South Asian females and there were no differences in Factor XII levels in male populations. These results suggest that elevated PAI-1 and fibrinogen in Asians of both genders may contribute to the increased vascular risk experienced in this population; however, the role of dyslipidaemia and Factor VII are not clear in these processes.

High prevalence of complement C7 deficiency among healthy blood donors of Moroccan Jewish ancestry.

The incidence of the specific component deficiencies in various ethnic groups is not known, although there appears to be an ethnic predilection for C6 and C8alpha-gamma deficiencies in blacks, whereas C7 and C8beta deficiencies are predominantly noted in Caucasians. Infectious diseases, particularly recurrent meningococcal infections, are observed more commonly with late component deficiencies. In the current study, we have simplified the PCR technique by using site-directed mutagenesis and designer primers in a cohort of Israeli Moroccan Jewish blood donors to ascertain allele frequency in this ethnic group, which, based on earlier studies, was considered to be at risk for C7 deficiency. The total mutant allele frequency in this ethnic cohort was 1.1% of a total of 365 healthy Israeli Moroccan Jews, including one homozygote. The identification of mutant alleles was efficient and inexpensive, and hence a large cohort was studied. The finding of complement deficiency identifies individuals at risk for Neisserial infections, which are known to be potentially life-threatening. Conversely, when a patient of Moroccan ancestry is diagnosed with a Neisserial infection, it is important to determine the complement status.

Prevalence of factor V Leiden in African-Americans.

Factor V Leiden (FVL) refers to a mutation on the clotting factor, Factor V. Protein C is a factor involved in the fibrinolytic pathway. Activated protein C (APC) normally degrades activated Factor V. The presence of the Leiden mutation on Factor V makes this protein resistant to degradation by APC, leading to a hypercoagulable state. Previous studies reported a prevalence of FVL in various populations between 0-6% and absent in Africans. We studied two factor V alleles from one hundred random blood samples submitted for CBC. DNA was extracted, PCR was performed for wild-type allele and Leiden mutation with GH internal control for both reactions, and agarose gel electrophoresis was performed. Of 100 samples, five were heterozygous for FVL, which is in accord with other reports. Interestingly, four of 70 samples (5.8%) from African-Americans were positive for the mutation. The study indicates an apparent prevalence of 5% in the Newark, New Jersey population, including African-Americans.

Factors determining the maintenance dose of warfarin in Chinese patients.

Chinese patients are reportedly more sensitive than Caucasians to the anticoagulant effect of warfarin. We examined warfarin dose requirements and their determinants in 151 Chinese out-patients on stable maintenance dose of warfarin with international normalized ratio of 2 to 2.5. Mean daily warfarin requirement was 3.3 +/- 1.4 mg, much lower than reported doses in Caucasian patients. The most important determinant was age (r = -0.43, p < 0.001), with progressively lower warfarin requirement with increasing age (p = 0.0001). There was a weaker association with body weight (r = 0.20, p = 0.01). Patients with chronic rheumatic heart disease tended to require a smaller dose than those with heart valve replacements (2.94 +/- 1.24 vs. 3.69 +/- 1.42 mg, p < 0.01). We confirm that Chinese patients require a smaller dose of warfarin for the same degree of anticoagulation. Age is the most important factor affecting dose requirement, although body weight and underlying disease also play a role.