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Since the introduction of PCC for treatment of bleeding episodes in hemophiliacs with inhibitors in 1972, many anecdotal reports and uncontrolled observations have been published, often with conflicting reports of efficacy. To date, three controlled double blind studies have been completed in which PCC have been evaluated. In each of the three studies acute hemarthrosis has been the only (Lusher et al 1980; Lusher et al 1983) or the predominant (Sjamsoedin 1981) type of bleeding evaluated. While acute joint bleeding lends itself well to clinical trial, there are recognized problems in evaluating response to treatment. Despite these limitations, it is noteworthy that non-activated PCC were found to be effective in approximately 50% of episodes in all three trials. Future trials are now being planned in an attempt to determine the role of activated PCC in the management of bleeding episodes in hemophiliacs with inhibitors. In the design of these trials, possible modifications to be considered are the exclusion (or separate randomization) of chronically disabled or "target" joints, more than one dose of unknown product, and longer periods of assessment.

Treatment of hemophilia, although greatly improved in recent years, continues to be problematic owing to infectious complications of blood product replacement therapy. This report examines the therapeutic options presently available for the treatment of hemophilia, focusing on the potential for repeated viral exposure to influence the progression of infectious disease, decreased risks of viral transmission with blood products produced using newer viral inactivation procedures, higher economic costs of newer blood products, and the current inadequate supply of blood products in the United States.

The response to a highly purified concentrate of porcine factor VIII was evaluated in 45 bleeding episodes in 38 patients with high responding inhibitor antibodies to factor VIII. A total of 437 infusions were given. The patients came from 25 hemophilia centers in the United States. The majority had a life- or limb-threatening hemorrhage for which other modalities had not been successful. In 32 of 45 episodes, a good to excellent response was obtained. Adverse reactions were minimal, occurring in 17 treatment episodes, and were mostly treated with antihistamines and/or hydrocortisone. No clear predictor of clinical response to porcine factor VIII concentrate was identified, including pretreatment human and porcine inhibitor levels, percentage of cross-reactivity between the human and porcine antibodies, and the presence of measurable levels of factor VIII after the porcine factor concentrate was given. Anamnesis to porcine factor VIII did occur in some instances. Porcine factor VIII is a valuable modality in the treatment of serious hemorrhages in patients with inhibitors to factor VIII. Its use should be considered early in the course of severe hemorrhage in these patients.

The structural physiology of the human spleen is discussed in depth here, with particular emphasis on the interrelationships between blood cells and the spleen. The unique microvasculature and structural relationships of the spleen form the basis for a number of functions important in both health and disease. Utilizing scanning electron microscopy one can visualize the interactions between blood elements and the spleen---the passage of deformable erythrocytes through narrow slits in the endothelium separating cord and sinus, the trapping of less deformable cells in the cords, the culling and pitting of abnormal or inclusion-bearing erythrocytes by splenic macrophages, as well as the sites of interaction between antigenic stimuli such as pneumococcal organisms and the T and B cells of the spleen.

Idiopathic thrombocytopenia purpura-(ITP) in children is generally a benign, self-limited process with spontaneous recovery occurring within a matter of days or weeks. Management remains somewhat controversial to date, however, and the controversy surrounding the use or nonuse of corticosteroids will no doubt continue until critical data become available. At present, there is little or no evidence to support the claim that steroids shorten the natural course of the disease. Furthermore, evidence that steroids lessen the risk of intracranial hemorrhage is conspicuously lacking. The authors no longer use steroids in ITP; however, if one does elect to use steroids, a selective approach based on an assessment of the severity of the bleeding tendency is recommended.

In view of uncontrolled observations and anecdotal reports suggesting that the activated PCC, Autoplex, was much more effective than standard (non-activated) PCC in controlling bleeding in hemophiliacs with inhibitors, a controlled double-blind study was designed to compare the effectiveness of Autoplex and Proplex. Acute hemarthrosis was chosen for study as this common but non-life-threatening lesion lends itself well to controlled study. A single dose of "unknown" product (Autoplex 75 FECU/kg; Autoplex 50 FECU/kg; or Proplex 75 FIX U/kg) was given, and effectiveness was judged at 6 hr. By all criteria of efficacy, there were no significant differences between the products. It is noteworthy that a single dose of PCC was judged effective in 50% of episodes, a figure that is consistent with other published clinical trials. In this model, no additional benefit was derived from using the activated PCC, Autoplex, in either dosage.

Acute ITP in children under 13 years of age is generally a benign, self-limited condition with spontaneous recovery occurring within a matter of days or weeks. Our analysis of platelet data indicate no advantage in terms of rate of recovery when steroids are used. In fact, the median of 3 weeks and mean of 3 1/2 weeks from onset to recovery in the nonsteroid-treated children were significantly better than the corresponding figures in the steroid-treated group. In addition, while reducing the risk of intracranial hemorrhage is generally given as the chief therapeutic rationale for using steroids, we have not seen a single case of ICH among 465 consecutive cases of acute ITP in children, the majority (93%) of whom did not receive steroids. On the other hand, adolescents, as adults, with ITP often have the autoimmune (chronic) form of the disease. In this group, corticosteroids may be of at least transient benefit and should be used.