The prothrombin time (PT) and the International Normalized Ratio (INR) were normal (12.2 seconds and 1.1, respectively). At the time of admission, the patient’s haemoglobin levels ranged around 6 g/dl, with mildly elevated white cell and low platelet counts (9,100/μl and 127,000/μl, respectively). A new non-resolving traumatic right lower extremity haematoma secondary to a fall prompted a transfer to our institution for further management. The patient had no personal or family history of a bleeding disorder. Notably, anaemia and bleeding persisted even after the discontinuation of apixaban, necessitating several hospital re-admissions, involving the transfusion of multiple units of packed red blood cells and fresh frozen plasma, as well as the administration of prothrombin complex concentrates and FVIIa-bypassing agents.
COUMADIN ANTI STROKE SKIN
Although information regarding bleeding sites was not clear from the outside medical records, it appeared that most bleeding was musculoskeletal and skin related (ecchymoses). The patient was on chronic anticoagulation with apixaban 2.5 mg every 12 hours (Eliquis ®, Bristol Myers Squibb, New York, NY, and Pfizer, New York, NY, USA) for stroke prevention. Due to coronavirus disease (COVID)-19 restrictions and complications of care, emicizumab offered an effective and convenient therapy, not only sparing the need for continued and intensified inhibitor eradication, but also allowing anticoagulation for stroke prophylaxis.Ī 79-year-old man with a history of multiple comorbidities, including atrial fibrillation, diabetes mellitus and rheumatoid arthritis, was admitted to an outside hospital due to symptomatic anaemia associated with bleeding, thought to be anticoagulation related. Here we present a case of AHA with a high titre inhibitor in a patient with extensive comorbidities and atrial fibrillation in whom inhibitor eradication could not be achieved within a few weeks using corticosteroids alone.
COUMADIN ANTI STROKE SERIES
With respect to AHA, there are several encouraging case reports, as well as a recent case series demonstrating efficacy. Emicizumab has been shown to be highly effective in controlling bleeding in patients with congenital haemophilia A and inhibitors, as demonstrated by the Haven Clinical Trials Series. Emicizumab is a bispecific antibody mimicking FVIII co-factor activity and is administered subcutaneously in weekly, biweekly or monthly intervals depending on dosing. Most recently though, the approval of emicizumab (Hemlibra ®, Genentech, South San Francisco, USA) for congenital haemophilia A with or without inhibitors against FVIII, has opened new avenues for the management of AHA. In fact, infections and sepsis are the most prominent contributors to morbidity and mortality in this population. Moreover, immunosuppression in elderly and frail patients is associated with a considerable number of adverse effects, ranging from 25% to 44%, with infections and sepsis being most common. Unfortunately, immunosuppression for inhibitor eradication is not always successful and may take many weeks or even months, with failure rates as high as 30–40%. Hence, rapid inhibitor eradication has been considered critical to enable the discontinuation of clotting factor support. These clotting factor products have relatively short half-lives (2–10 hours), requiring frequent infusions and indwelling lines making them unsuitable for long-term management in the elderly at home or in long-term care facilities. The currently approved products to curb bleeding are FVIIa-based bypassing agents (Novo7 ®, Novo Nordisk, Bagsvaerd, Denmark FEIBA ® and recombinant porcine (rp) FVIII (Obizur ®), both from Takeda, Lexington, KY, USA. Inhibitor eradication has been deemed a cornerstone in the management of AHA, since long-term bleed control in the presence of inhibitors against FVIII is difficult to achieve in most patients. Inhibitor eradication involves immunosuppression using immune modulators such as corticosteroids or rituximab (Rituxan ®, Genentech, South San Francisco, USA), as well as cytotoxic drugs such as cyclophosphamide (Cytoxan®, Bristol-Meyers Squibb, Deerfield, IL, USA), administered alone or in combination. To date, the management of AHA consists of two aspects, namely inhibitor eradication and bleed control. In addition, AHA is often associated with malignancy complicating the management of this disorder. AHA predominantly affects the elderly, who are often burdened with a considerable number of comorbidities. AHA is characterized by severe, often life-threatening bleeding associated with a high mortality rate. Acquired haemophilia A (AHA) is a rare haemorrhagic disorder caused by the development of autoantibodies inhibiting factor VIII (FVIII) function (a.k.a.
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