Venous thromboembolism prophylaxis of a patient with MYH-9 related disease and COVID-19 infection:A case report

BACKGROUND The May-Hegglin anomaly is among a group of genetic disorders known as MYH9-related disease.Patients with inherited platelet disorders such as May-Hegglin anomaly are at a variably increased risk for bleeding due to a combination of platelet dysfunction and thrombocytopenia.Patients admitted to the hospital with coronavirus disease 2019(COVID-19)infection are at an increased risk for a venous thromboembolism event(VTE).The National Institutes of Health COVID-19 treatment guidelines recommend using a prophylactic dose of heparin as VTE prophylaxis for adults who are receiving high-flow oxygen.We describe a patient admitted for COVID-19 infection with pneumonia and a history of May-Hegglin anomaly.The patient presented a challenge to determine prophylactic anticoagulation as there are no clear guidelines for this patient population.CASE SUMMARY Herein,we describe the case of a 39-year-old woman admitted with acute hypoxic respiratory failure secondary to COVID-19 pneumonia.She had a history of May-Hegglin anomaly and demonstrated risk for bleeding since childhood,including a life-threatening bleeding event at the age of 9 years requiring blood and platelet transfusions.Her baseline platelet count was 40-50×109/L throughout her adult life.Her family history was also notable for May-Hegglin disorder in her mother,maternal uncle,maternal grandfather and her son.Computed tomography/pulmonary angiography revealed bilateral consolidative opacities consistent with multifocal pneumonia.Complete blood count was notable for platelet count of 54×109/L.She was admitted for inpatient respiratory support with high-flow oxygen per nasal cannula and was managed with guideline-directed therapy for COVID-19,including baricitinib and dexamethasone.The Hematology/Oncology consultation team was requested to assist with management of VTE prophylaxis in the setting of active COVID-19 infection and an inherited bleeding disorder.After review of the literature and careful consideration of risks and benefits,it was decided to treat the patient with prophylactic enoxaparin.She was closely monitored in the hospital for bleeding and worsening thrombocytopenia.She had no bleeding or signs of VTE.Her respiratory status improved,and she was discharged home after 5 d of hospitalization with supplemental oxygen by nasal cannula and dexamethasone.At the 6-month follow-up,the patient successfully discontinued her home oxygen use after only a few weeks following discharge.CONCLUSION The patient presented a challenge to determine prophylactic anticoagulation as anticoagulation guidelines exist for patients with COVID-19,but there are no clear guidelines for management of patients with COVID-19 and inherited bleeding disorders,particularly those with MYH9-related disease.She was discharged after recovery from the COVID-19 infection without bleeding or thrombosis.As there are no published guidelines for this situation,we present a pragmatic,informed approach to a patient with MYH9-related disease who had an indication for anticoagulation.

African origins and chronic kidney disease susceptibility in the human immunodeficiency virus era

Chronic kidney disease （CKD） is a major public health problem worldwide with the estimated incidence growing by approximately 6% annually. There are striking ethnic differences in the prevalence of CKD such that, in the United States, African Americans have the highest prevalence of CKD, four times the incidence of end stage renal disease when compared to Americans of European ancestry suggestive of genetic predisposition. Diabetes mellitus, hypertension and human immunodeficiency virus （HIV） infection are the major causes of CKD. HIV-associated nephropathy （HIVAN） is an irreversible form of CKD with considerable morbidity and mortality and is present predominantly in people of African ancestry. The APOL1 G1 and G2 alleles were more strongly associated with the risk for CKD than the previously examined MYH9 E1risk haplotype in individuals of African ancestry. A strong association was reported in HIVAN, suggesting that 50% of African Americans with two APOL1 risk alleles, if untreated, would develop HIVAN. However these two variants are not enough to cause disease. The prevailing belief is that modifying factors or second hits （including genetic hits） underlie the pathogenesis of kidney disease. This work reviews the history of genetic susceptibility of CKD and outlines current theories regarding the role for APOL1 in CKD in the HIV era.