Apparent cellulitis with a prolonged APTT

Ganesh C Kudva, MD MRCP,1 Murali Sundaram, MD,2 and J Heinrich Joist, MD PhD1,3

1 Department of Internal Medicine, Saint Louis University School of Medicine, St Louis, MO, USA, 2 Department of Radiology, Saint Louis University School of Medicine, St Louis, MO, USA, 3 Department of Pathology, Saint Louis University School of Medicine, St Louis, MO, USA

Correspondence to: Dr Ganesh C Kudva, Division of Hematology and Oncology, Saint Louis University Cancer Center, 3655 Vista Avenue, St Louis, MO 63110-2539, USA

E-mail: kudvagc@slu.edu

The differential diagnosis of cellulitis includes haematoma. This can be the presentation of a bleeding disorder in adult life.
Case History

A man of 38 with HIV infection reported painful swelling and redness in his left shoulder and upper arm for the past three days, without fever. There had been no trauma. Medications for HIV infection included stavudine, lamivudine and indinavir. On examination there was moderate erythema and swelling over the painful area; his temperature was normal.
Routine blood and urine tests were unremarkable. In a coagulation screen, performed as part of a ‘sepsis panel’, activated partial thromboplastin time (APTT) was mildly prolonged at 46 s (normal 23.3-32.6); prothrombin time was normal. Radiographs of the left shoulder and upper arm showed nothing of note. Blood was obtained for culture and he was started on intravenous ampicillin/sulbactam for presumed cellulitis. MRI of the left upper limb on day 2 revealed changes interpreted as oedema of the subcutaneous tissue, biceps and triceps (Figure 1).

After five days of antibiotic therapy there was no appreciable improvement in the shoulder and arm. Blood cultures were negative. Repeat APTT was 51 s. Exploratory surgery for a possible abscess on day six revealed a 3 × 7 cm organizing haematoma of the left biceps which was evacuated. Microbial stains and cultures from the haematoma were negative. On further evaluation factor VIII proved to be 6U/dL (normal > 50), a screening test for APTT inhibitor was negative (50-50 mix with 1 h incubation) and lupus anticoagulant was not detected. Work-up for von Willebrand disease was negative. The haematologist elicited a history of large haematoma formation after inguinal herniorraphies at ages 16 and 35 and prolonged oozing after dental extraction at age 26, controlled without blood or blood product administration. In addition the patient reported that a maternal cousin had a bleeding disorder, undiagnosed. The patient was given 3000 units of monoclonal factor VIII concentrate and four additional doses of 1500 units at 12-hour intervals. There was no further bleeding. The erythema and swelling of the left shoulder and arm resolved promptly.

Comment

This case raises several important issues. First, differential diagnosis of cellulitis, immediately suspected because the patient was known to be immunocompromised, should have included venous thrombosis and haematoma and steps should have been taken to rule out these conditions1. Second, the history of recurrent abnormal bleeding was missed because detailed questions about abnormal bleeding after trauma or surgery were apparently not asked. Patients with mild bleeding disorders frequently do not volunteer and may even deny having had ‘abnormal’ bleeding, since abnormal is not easily defined and mild bleeding episodes may not trigger spontaneous recall. Furthermore, with mild and moderate bleeding disorders, excessive bleeding may not be serious enough to require transfusion of blood or blood components and may not occur with all injuries or surgical procedures. Third, the prolonged APTT found on routine, initial laboratory evaluation should have been properly evaluated, particularly in this afebrile patient without leukocytosis who did not respond to antibiotic therapy. Causes of selective (normal prothrombin time) APTT prolongation include artifacts due to inappropriate blood collection, processing and plasma storage, heparin, and deficiency of or inhibitor to coagulation factors VIII, IX, XI, XII, high-molecular-weight kininogen or kallikrein and lupus anticoagulants2. Lupus anticoagulants are commonly found in HIV infection but are generally not associated with abnormal bleeding; nor do they seem to be associated with venous or arterial thrombosis, as they are in individuals without HIV3.

The incidence of haemophilia A is 1 per 5000-10 000 male live births. Mild haemophilia A (factor VIII > 5U/dL <>4. It is not infrequently diagnosed late in life, as in this case, usually after abnormal bleeding with trauma or surgery5. In this case there was no history of trauma.

References

1.
Bates B. An approach to symptoms—the peripheral vascular system. In: Bates B, ed. A Guide to Physical Examination and History Taking, 3rd edn. Philadelphia: Lippincott, 1990: 60.

2.
Bajaj SP, Joist JH. New insights into how blood clots: implications for the use of APTT and PT as coagulation screening tests and in monitoring of anticoagulant therapy. Semin Thromb Hemost 1999;25: 407-18 [PubMed].

3.
Perkocha LA, Rodgers GM. Hematologic aspects of human immunodeficiency virus infection: laboratory and clinical considerations. Am J Hematol 1988;29: 94-105 [PubMed].

4.
Koumbarelis E, Rosendaal FR, Gialeraki A, et al. Epidemiology of hemophilia in Greece: an overview. Thromb Haemost 1994;72: 808-13 [PubMed].

5.
Roberts HR, Hoffman M. Hemophilia A and hemophilia B. In: Beutler E, Lichtman MA, Coller BS, Kipps TJ, Seligsohn U, eds. Williams Hematology, 6th edn. New York: McGraw-Hill, 2001: 1639-57.

Journal of the Royal Society of Medicine