When the Cause of Hematomas in Anticoagulated Patients is Not Anticoagulants – Case Report
Not every bleeding during anticoagulation, especially if within the therapeutic range, can be attributed to this treatment. Particularly in older individuals and the presence of typical extensive hematomas, it is necessary to consider another cause, such as acquired hemophilia A. The following case report illustrates how such a case can be detected and what can be done to improve the patient's prognosis.
Medical History
A 78-year-old man visits the general practitioner (GP) with an extensive hematoma on his right thigh and both underarms, walking with two French crutches (post-injury). He also has smaller hematomas under his knees. He does not report any falls.
In the family history, there is no known inclination to bleeding. His parents are deceased, his brother is alive without issues, and neither of his adult children has any medical conditions.
From an internal perspective, he is being treated for arterial hypertension, diabetes mellitus (DM), atrial fibrillation (AF), and hypercholesterolemia. His medication includes amiodarone, bisoprolol, metformin, atorvastatin, and warfarin. He also has renal insufficiency due to DM (CrCl 42 ml/min). He has been on warfarin for AF for 7 years. His INR is monitored by the GP and is mostly within the therapeutic range. If not, the warfarin dose is minimally adjusted up or down. His current dosage is 2 mg daily.
A complete blood count (CBC) and INR were performed. The CBC shows only mild anemia typical of chronic disease, with a drop in Hb by 25 g/l and an INR result of 2.7. CBC: Leu 8.10 × 109/l; RBC 2.38 × 1012/l; Hb 75 g/l; HCT 0.2; MCV 87 fl; Plt 151 × 109/l.
GP's recommendation: Discontinue warfarin for 3 days with INR monitoring.
Urgent Admission and Diagnostics
Two days later, the patient was brought to the emergency department due to weakness and exertional dyspnea. Hematomas appeared on his right arm, and the hematoma on his right thigh enlarged. Physical examination revealed pale visible mucous membranes, irregular heart action at 115/min, and BP 95/60 mmHg. Laboratory tests showed further drop in Hb to 65 g/l, INR of 2.0, but an aPTT of 84 s (patient)/34 s (control).
The patient was admitted to the ICU of the internal clinic and underwent follow-up laboratory tests upon admission. CBC: Leu 10.0 × 109/l; RBC 2.22 × 1012/l; Hb 65 g/l; HCT 0.2; MCV 87 fl; Plt 345 × 109/l. In coagulation tests, thrombin time was normal, INR 1.95, but aPTT was significantly prolonged: 93.9 s (patient)/33.1 s (control), with a P/K ratio of 2.8, and a 1:1 correction after 1 hour 53.7 s, after 2 hours 68.8 s.
Suspecting acquired hemophilia A (AHA), further tests confirmed FVIII activity of 0.9%, with an inhibitor level of 32.3 BU/ml, solidifying the AHA diagnosis.
Treatment Course
Treatment began immediately (patient weight = 95 kg) with rFVIIa (activated eptacog alfa) at a dose of 16 mg i.v. continuously for 24 hours. Vitamin K1 was administered at 3 mg i.v. to eliminate warfarin. For immunosuppressive therapy, cyclophosphamide (CF) 50 mg 2x1 and methylprednisolone 125 mg daily were given with glucose monitoring. Bleeding and overall condition gradually stabilized, supplemented with erythrocyte mass.
rFVIIa at 16 mg i.v. was given for 4 days, then reduced by half for 1 day and reduced again to a quarter the next day, then discontinued. The patient did not bleed further and was off anticoagulant therapy. After 10 days, aPTT values were minimally better, INR corrected, and the patient felt much better after anemia correction. However, these corticosteroid doses led to DM decompensation and the necessity to switch to insulin.
After 3 weeks of therapy, aPTT values improved (patient time 50.1 s, control 34.2 s), warranting FVIII and inhibitor testing: FVIII 25%, inhibitor titer 3.9 BU/ml.
We faced the following questions:
- How to proceed with immunosuppressive therapy? Considering DM, should we continue CF and quickly discontinue corticosteroids, or discontinue CF and taper corticosteroids slowly as usual?
- How to proceed with anticoagulant therapy? When to start, should it be standard dosing or lower due to a potential AHA relapse?
We opted to discontinue CF and reduce corticosteroids to 10 mg quickly, with DM stabilized on antidiabetic drugs and balanced glucose levels. The dose was later reduced to 5 mg prednisone outpatient and completely discontinued after 4 months.
Regarding anticoagulant therapy, we decided to initiate it when FVIII levels exceeded 30%, and the question was with what. Given CrCl fluctuating between 38 and 44 ml/min, we chose rivaroxaban at 15 mg daily.
There was also an investigation for the cause of AHA but unsuccessfully, concluding the diagnosis as idiopathic AHA.
In the following 2 years, the patient remained without bleeding and without a relapse of the condition. Unfortunately, further information is unavailable as he was admitted to a local senior center, according to GP.
Conclusion
This case study teaches that not every bleeding during anticoagulation, especially within the therapeutic range, can be attributed to this treatment. Particularly given the age and typical extensive hematomas, another cause, mainly AHA, must be considered. The risk of major to life-threatening bleeding is particularly high in such cases. Therefore, it is crucial to diagnose as soon as possible, discontinue anticoagulation, and initiate comprehensive AHA therapy. This always increases the chances of therapeutic success and further quality life for the patient during disease remission.
doc. MUDr. Petr Dulíček, Ph.D.
IV. Internal Hematology Clinic, Faculty of Medicine, Charles University and University Hospital Hradec Králové
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