JessicaH. Lewis

Corticosteroid Therapy for Acquired F VIII:C Inhibitors

The appearance of an acquired inhibitor to factor VIII clotting activity (F VIII:C) in a non‐haemophiliac is an uncommon phenomenon; but, when it occurs, represents a difficult therapeutic problem. Cyclophosphamide has been the most frequently used form of therapy while corticosteroids, when used alone, have been felt to be ineffective. During the past 25 years, 18 of these patients have been evaluated in Pittsburgh. Their mean age was 63·7 years. Nine were female and nine male. Sixteen of the 18 received corticosteroids as their primary form of therapy. Eleven of the 16 (69%) showed clinical and laboratory improvement. Seven of the 11 had a complete response and the remaining four a partial response. Five patients demonstrated no improvement with corticoid therapy. The time to response varied from 4 to 41 d (x̄ 15·8). It was concluded that corticosteroids when used alone provide therapeutic results comparable to immunosuppressive therapy in the treatment of acquired inhibitors to F VIII:C and therefore represent a therapeutic alternative to immunosuppressive agents.

ACQUIRED-IMMUNODEFICIENCY-LIKE SYNDROME IN TWO HAEMOPHILIACS

The immunological status of two multiply transfused patients with severe haemophilia A and diffuse lymphadenopathy was evaluated. But patients appeared clinically well and denied homosexuality or intravenous drug abuse. Immunological studies revealed depressed cellular immune function with anergy, relative lymphopenia, decreased T helper cells, and increased T suppressor cells in both patients and an altered T-helper-cell/T-suppressor-cell ratio in one. Hyperresponsiveness of the humoral immune system was demonstrated by elevated IgG and IgM. Lymph-node biopsy revealed benign nonspecific hyperplasia in both patients. The lymphadenopathy and immunological features in these two haemophiliacs bear a striking resemblance to the acquired immunodeficiency syndrome (AIDS) of homosexuals, intravenous drug abusers, and Haitian immigrants. These findings may represent a prodromal phase or a forme fruste of AIDS. Transmission of an infectious agent in blood products seems likely.

Chronic Liver Dysfunction in Multitransfused Hemophiliacs

Liver dysfunction and exposure to the hepatitis B antigen were assessed by serum transaminase (SGPT and SCOT) levels and HBsAg and anti‐HBs during a three year period in a group of 118 patients with factor VIII or factor IX deficiency. The 107 HBsAg negative patients were divided into four groups according to their mode of therapy. Persistently abnormal transaminase values were present in 51 per cent of patients with a large exposure to factor VIII concentrates, in 43 per cent with a small factor VIII exposure and in 37 per cent exposed to prothrombin complexes. This was contrasted with abnormalities in 8 per cent of patients treated only with cryoprecipitate. The incidence and degree of serum transaminase abnormality appeared independent of a past history of jaundice. All patients without persistent antigenemia who had been treated with pooled plasma products showed antibodies to HBsAg. High titer anti‐HBs prior to initial fraction therapy appeared protective against jaundice. The eleven patients with persistent antigenemia had significantly higher transaminase levels than the HBsAg negative group.

Disappearance of inhibitor to factor VIII in HIV‐infected hemophiliacs with progression to AIDS or severe ARC

The spontaneous disappearance of the inhibitor to factor VIII (FVIII) was observed in two human immunodeficiency virus (HIV)‐infected men with hemophilia A. Both men had end‐stage HIV infection, one with acquired immune deficiency syndrome (AIDS) and one with severe AIDS‐related complex (ARC). Loss of the inhibitor was associated with a fall in T4 helper lymphocytes to <100 per mm3 in both patients. Subsequent spontaneous and traumatic hemorrhages were treated successfully with standard doses of FVIII concentrate, resulting in adequate FVIII: C levels and good hemostasis. The mechanism by which the anti‐FVIII inhibitor disappears is not known, but it is likely to be related to a quantitative decline in T4 cell number.

Patterns of gastrointestinal hemorrhage in hemophilia

Peptic ulcer has been reported to be the cause of bleeding in 53%-85% of hemophiliacs with gastrointestinal hemorrhage (GIH). The management of GIH in hemophiliacs during the past decade has been affected by the availability of plasma concentrates, an increasing occurrence of chronic liver disease, and widespread use of endoscopic procedures. To determine the present patterns of GIH, we reviewed our experience at the Hemophilia Center of Western Pennsylvania during the last 10 yr. Twenty-five (10.3%) of 243 hemophiliacs experienced 41 episodes of GIH. The severity of hemophilia and a history of retroperitoneal hemorrhage were significant risk factors for GIH. Duodenal ulcer (22%), unknown site (22%), and gastritis (14%) were the three most common diagnoses. The use of fiberoptic endoscopy resulted in the recognition of diagnoses such as gastritis, esophagitis, Mallory--Weiss syndrome, and esophageal varices. Red cell transfusion requirements of hemophiliacs with GIH were no different than those of nonhemophiliacs with GIH (p greater than 0.05). The amount of factor VIII replacement used by hemophiliacs with GIH correlated with the severity of gastrointestinal bleeding (p less than 0.01), but not with the cause of gastrointestinal bleeding (p greater than 0.05). In conclusion, hemophiliacs develop GIH secondary to a variety of causes as do nonhemophiliacs. Fiberoptic endoscopy, after correction of factor VIII level to 0.40 U/ml, is a safe and valuable diagnostic procedure in hemophiliacs. The specific etiology of GIH in hemophiliacs should be aggressively sought and appropriate specific therapy provided.

Comparative hematology and coagulation: Studies on rodentia (Rats)

Blood from adult male Wistar rats clotted rapidly in glass or siliconized tubes; the clots retracted and did not lyse. The serum prothrombin, plasma prothrombin and activated partial thromboplastin times were shorter than those of normal humans. In contrast, the thrombin and reptilase times were longer than those of normal human plasma, due apparently to the presence of a low-grade thrombin inhibitor in rat plasma. Coagulation factors, X, VIIIR:vW and IX assayed lower in rat than human plasma, while factors VIII:C and anti-thrombin III were higher. Values for other coagulation factors (II, V, VII, XI, XII and Fletcher) fell within the human range. Platelets were small and numerous. They aggregated well with ADP but poorly or not at all with collagen, ristocetin, thrombin, epinephrine, arachidonic acid and pig or bovine plasmas. Leukocytes numbered 4-8 X 10(3) cells/mm3, a near human range and were predominantly lymphocytic. Erythrocytes were small (MCV = 56-60 fl) and numerous (5.5-6.4 X 10(6) cells/mm3).