Relative hemostatic effectiveness of human platelets stored at 4 degrees and 22 degrees C.

Platelet concentrates stored at 2 degrees to 4 degrees C or at 20 degrees to 24 degrees C for 24 or 72 hr were transfused to 22 thrombocytopenic patients selected to minimize host factors which affect the survival and function of transfused platelets. Platelets stored at either temperature range for only 24 hr were equally effective in elevating platelet levels and in shortening bleeding times, 1, 4 and 24 hr after transfusion. After 72 hr of storage, however, refrigerated platelets were significantly less effective than platelets kept at room temperature by these two criteria. We suggest that routine storage of platelets at 2 degrees to 4 degrees C can no longer be justified except possibly when platelets are to be shipped over long distance by common carrier and transfused within 24 hr of preparation.

Influence of HLA-A2 on the effectiveness of platelet transfusions in alloimmunized thrombocytopenic patients.

Platelet transfusions from donors selectively mismatched for cross-reactive and certain non-cross-reactive HLA antigens were found to be more effective in HLA-A2 negative than in HLA-A2 positive, alloimmunized thrombocytopenic patients. The two groups of patients responded equally well to platelets matched for antigens of the HLA-A and B loci. Certain alloimmunized patients negative for HLA-A2 continued to respond satisfactorily to platelets selectively mismatched for non-cross-reactive HLA antigens as long as platelets containing HLA-A2 were avoided. The data indicate that platelet transfusion support can be provided within a broader range of donor-recipient HLA antigenic disparity to HLA-A2 negative alloimmunized patients than to those who are positive for this antigen.

Successful transfusion of platelets "mismatched" for HLA antigens to alloimmunized thrombocytopenic patients.

A critical factor limiting the availability of histocompatible platelet transfusions for alloimmunized, thrombocytopenic patients is the large pool of HLA-typed donors needed to procure platelets perfectly matched for HLA antigens. We have, therefore, investigated the effectiveness of platelets obtained from donors having lesser degrees of histocompatibility. In 421 transfusions administered to 59 alloimmunized patients who were refractory to "random donor" platelets, it was found that platelets mismatched for 1 or 2 "cross-reactive" HLA antigens were in most instances as effective in increasing circulating platelet levels as perfectly matched platelets. A significant number of patients also responded to platelets from donors selectively mismatched for non-cross-reactive HLA antigens. The latter group had a significantly reduced frequency of the antigen HLA-A2 (13%) in comparison to the total patient population (49%). Use of donors whose HLA antigens are serologically cross-reactive with those of alloimmunized patients provides approximately 10 times as many prospective donors as does selection based on matching for HLA and simplifies the procurement of hemostatically effective platelets for such patients.

Predictive value of cross-matching for transfusion of platelet concentrates to alloimmunized recipients.

Compatibility tests in which donor platelets were tested with recipient sera were performed retroactively after 64 transfusions of platelets from 59 unrelated donors to 10 alloimmunized patients. Techniques used were serotonin release, aggregometry, platelet factor 3 release, and lymphocytotoxicity, each of which has been advocated as a means of testing donor-recipient platelet compatibility. Although "false positive" reactions were few (positive crossmatch but satisfactory transfusion response), "false negative" reactions (negative crossmatch but poor transfusion response) were unacceptably high (43% by lymphocytotoxicity, 60% by serotonin release, 76% by platelet factor 3 release, and 83% by aggregometry). We conclude that current methods of detecting isosensitization to platelet alloantigens are less satisfactory than HLA phenotyping in selecting unrelated platelet donors for an alloimmunized patient population.

Hereditary antithrombin III deficiency and thromboembolic disease.

Two teenage brothers with recurrent thromboembolic disease were found to have antithrombin III deficiency. A family study spanning four generations revealed a total of 10 members with antithrombin III deficiency. Five of the 10 affected family members have had thrombotic problems. Antithrombin III deficiency was documented by coagulation assays measuring heparin cofactor, anti-Factor Xa, and progressive antithrombin activity; the level of antithrombin III antigenic material measured by immunoelectrophoresis was low in subjects with abnormal coagulation assays. The clinical features which may lead one to suspect the hereditary hypercoagulable condition of antithrombin III deficiency are reviewed.

The effect of platelet concentrate storage temperature on adenine nucleotide metabolism.

The effect of platelet concentrate storage temperature (4 degrees C versus 22 degrees C) on platelet adenine nucleotide metabolism was studied. In general, levels of platelet ATP and ADP, the release reaction, and the metabolis nucleotide pool were best preserved for 72 hr by storage of concentrates at 4 degrees C. Storage of concentrates for 72 hr at 22 degrees C was occasionally associated with a pH decrease to less than 6.0, which is incompatible with platelet viability. When the pH fell below 6.0, there was a marked deterioration of platelet adenine nucleotide levels and the release reaction. The results for concentrates stored at 22 degrees C, with a final pH above 6.0, were not inferior to the results for those stored at 4 degrees C. The pH remained above 7.0 in all concentrates stored at 4 degrees C. The pH changes of platelet concentrates stored at 22 degrees C could not solely be attributed to platelet count, red cell count, or bacterial contamination. Storage at both temperatures was associated with conversion of ATP in the metabolic adenine nucleotide pool to hypoxanthine.

Studies of fibrinogen measurement in the CAP survey program.

A review of the College of American Pathologists' Surveys experience in fibrinogen testing from 1967 to 1974 is reported. Trends in fibrinogen methodology and the emergence of a consensus choice of the modified thrombin time method are documented. The reasons for these changes from former methods are discussed.

Hereditary thrombocytopenia, deafness, and renal disease.

The syndrome of hereditary thrombocytopenia, deafness, and renal disease was manifest in at least eight members in three generations of a family. They had a lifelong history of bleeding, usually as epistaxis, bilateral sensorineural deafness starting in late childhood or the teenage years, and persistent proteinuria with varying degrees of renal dysfunction. Two members died at a young age, one from central nervous system hemorrhage, the other from chronic renal failure. Splenectomy and steroid therapy have been of transient benefit. There was dominant inheritance of the syndrome. Hematologic studies showed thrombocytopenia, large platelets, and megakaryocytic hyperplasia of the bone marrow. In contrast to a previous report, our studies showed that affected members had normal in-vitro platelet function and normal ultrastructural platelet morphology. At autopsy, histologic changes in the kidney of one affected family member were indistinguishable from those reported in classic hereditary nephritis with nerve deafness (Alport's syndrome).