1/16/18 Resident Morning Report – Arm Swelling, Bruising, and Pain Secondary to Coagulopathy Caused by Acquired Factor VIII Inhibitor

CC: Left Arm Swelling and Pain

HPI: 84 y/o Caucasian male with history of CAD s/p CABG, HTN, HLD, CKD stage 2, and BPH presented with a 2 day history of swelling and excruciating pain in the L arm following a routine lab draw from a vein in the L hand. Swelling had begun at the site and expanded to include the entirety of his arm. Overlying bruising emerged with increasing pain. He also noted bruising of the internal thighs incidentally but denied trauma at either site. He had not history of bleeding diathesis diagnosed in him or a family member and had no reported easy bruising or bleeding previously. He had no recent medication changes. Physical exam was notable for a swollen and tender L arm with erythema and extensive ecchymoses extending from the wrist to the elbow. Range of motion was intact as were peripheral pulses, even in the affected arm. Notably, the patient had bruising on the extremities and on his trunk and abdomen. Physical exam was not concerning for compartment syndrome of the arm given the aforementioned findings, though the team closely monitored for signs of impending arterial compression. Initial laboratory evaluation revealed an elevated partial thromboplastin time (PTT) but a normal prothrombin time (PT) and international normalized ratio (INR). Mixing studies were performed, and the PTT did not correct suggesting the presence of an inhibitor. Factor VIII levels were checked and were significantly lower than the lower limit of normal. Factor VIII inhibitor level was detected at 35 Bethesda Units. This confirmed the presence of an acquired factor VIII inhibitor.


Morning Report Pearls:

Bleeding disorders can be divided primarily into broad categories, those that affect primary hemostasis and those that affect secondary hemostasis. Disorders of both primary and secondary hemostasis can be either acquired or inherited.

Some Causes of Primary Hemostatic Disorders, Acquired

  • Thrombocytopenia (many causes including ITP, TTP, etc.)
  • Cirrhosis
  • DIC or Sepsis
  • Malignancy, especially leukemia or lymphoma
  • Myeloproliferative or Myelodysplastic Disorders
  • Uremia
  • Medications/Drugs, including NSAIDs, aspirin, etc

Some Causes of Primary Hemostatic Disorders, Inherited

  • von Willebrand Disease
  • Congenital Afibrinogenemia
  • Genetic Platelet Disease, including Wiskott-Aldrich Syndrome, Bernard-Soulier Disease, Glanzmann Thrombasthenia

Some Causes of Secondary Hemostatic Disorders, Acquired

  • Vitamin K Deficiency
  • Medications, including Warfarin and Heparin
  • Liver Failure or Cirrhosis
  • DIC or Sepsis
  • Fat Malabsorption
  • Acquired Factor Deficiencies, including Acquired Factor VIII Deficiency
  • Malignancy, especially leukemia or lymphoma

Some Causes of Secondary Hemostatic Disorders, Inherited

  • Hemophilias (A, B, or C)
  • Cystic Fibrosis Resulting in Malabsorption

When evaluating a patient with a suspected bleeding disorder, physical exam can be very informative in narrowing the diagnosis. Patients with primary hemostatic disorders (platelets) tend to present with mucosal or cutaneous bleeding; epistaxis or gingival bleeding; petechiae, especially in dependent areas; immediate bleeding post-injury; and menorrhagia/metomenorrhoagia. Patients with secondary hemostatic disorders (coagulation factors) tend to present with large palpable ecchymoses; hemorrhage into joints or muscles; delayed bleeding given preservation of platelet function and number; and post-operative bleeding.

Secondary hemostatic disorders affect PT, INR, and PTT depending on the factors involved. Whenever PT or PTT are affected due to concern for bleeding diathesis, a mixing study is appropriate. In this case, PTT was prolonged. An example of a PTT mixing study is below:

The results of this mixing study led to concern for an acquired Factor VIII inhibitor, which was confirmed. Of note, lupus anticoagulant was ruled out on lab testing.

Causes of Acquired Factor VIII Inhibitor

  • Malignancy
  • Pregnancy
  • Autoimmune Disease (including SLE)
  • Clonal Lymphoproliferative Disorders

11/9/16 Resident Morning Report – Hemarthrosis, Acquired Factor VIII Inhibitor

CC: 2 days of L knee pain and swelling

ID: 58 yo homeless male with alcohol abuse and seizure disorder presents with 2 days of L knee pain and swelling.  He reports a history of frequent falls (while intoxicated) and increased joint swelling after these falls over the past 4-5 months.  Exam was notable for diffuse L knee swelling, full ROM, stable varus/valgus maneuvers, negative posterior drawer test with improvement in pain with passive motion.  Joint fluid analysis demonstrated markedly bloody red fluid with 1,333 nucleated cells, 25% neutrophils, 40% lymphocytes, 29% monocytes, and 6% eosinophils.  Labs were notable for Hgb of 8.8, Plts of 384, and PTT of 84 secs which did not correct on mixing study – subsequent workup with a Factor VIII inhibitor assay was remarkable at 760 Bethesda Units.  Patient was ultimately found to have a renal cell carcinoma (RCC) and diagnosed with hemarthrosis likely secondary to acquired Factor VIII inhibitor from his underlying RCC.

synovial-joint-fluid-analysis

Joint Fluid Analysis (PDF)

 


Pearls from morning report:

  • Causes of bloody joint effusions include: hemophilia, trauma, malignancy, Charcot joint, and arteriovenous malformations.
  • Causes of acquired factor inhibitors include: pregnancy, malignancy, drugs,

Random trivia:

The lupus anticoagulant antibody was identified by our very own Dr. Donald Feinstein in 1972.  Dr. Feinstein continues to round with our hematology consult service here at LAC+USC!


Want to read more?

Acquired haemophilia: an overview for clinical practice (European Journal of Haematology)
How I manage patients with acquired haemophilia A (British Journal of Haematology)


References: 

Siva C, Velazquez C, Mody A, Brasington R. Diagnosing acute monoarthritis in adults: a practical approach for the family physician. Am Fam Physician. 2003;68(1):83-90.