Paul Holland: contributions to transfusion medicine.

Paul Holland began his career in transfusion medicine in 1963 as an assistant to Dr. Paul Schmidt in the Blood Bank at the National Institutes of Health (NIH). He served at the NIH for 20 years and retired in 1983 with the rank of Captain in the Public Health Service. He subsequently became the Medical Director/CEO of the Sacramento Medical Foundation Blood Center, now Blood Source, a position he held for the next 21 years. Paul Holland has authored/co-authored 265 articles, chapters and monographs, mostly concerning issues relating to either viral hepatitis or HIV. In addition to his research career, Paul was a very active educator, having contributed importantly to the development of many current thought leaders in transfusion medicine. His distinguished career also included important administrative roles in national and international organizations relevant to transfusion medicine. He also was the recipient of many honors and awards which has won him wide-spread renown and the respect of his many colleagues.

The original blood group pioneers: the Hirszfelds.

Ludwik Hirszfeld, together with his wife Hanka, was the first to study the blood groups in large numbers of subjects (soldiers) during World War I at the Macedonian front. They found significant differences in the distribution of the ABO blood groups, that is, type A was more common in soldiers from North Central Europe, whereas type B was more common in those from Eastern Europe. Their data were later (in the 1920s and 1930s) misused by German nationalists to support the concept of Aryan supremacy. The Hirszfelds also discovered Salmonella paratyphi C, now known as Salmonella hirzfeldi. Their landmark studies drew others to this new field of seroanthropology, most notably Arthur Mourant, as well as Robin Race and Ruth Sanger, who wrote "Blood Groups in Man" detailing the antigenic differences among various peoples.

Sickle cell disease: two fatalities due to bone marrow emboli in patients with acute chest syndrome.

Acute chest syndrome (ACS) in patients with sickle cell disease (SCD) is a common complication contributing to death. ACS can present as sudden, unexpected death, and the medical history of SCD may not be immediately available for the medical examiner. Forensic implications for ACS are more likely to be encountered in patients with the HgbSC variant of SCD because the presence of a spleen may obscure recognition of SCD. Pathologists commonly observe small bone marrow emboli within the lung vasculature postmortem after trauma or vigorous cardiopulmonary resuscitation. Consequently, the finding of pulmonary marrow emboli in ACS may be dismissed as incidental and nonpathologic. Pulmonary marrow emboli cause ACS in patients with SCD, when there is parvoviral infection with marrow necrosis. Pulmonary marrow embolism in ACS has special significance in forensic pathology. Forensic pathologists investigate sudden, unexpected deaths during exertion, such as athletics, police pursuit, or military training. A causal relationship linking sickling hemoglobinopathy with physical exertion and sudden death has been reported. In the absence of a specific and timely medical history of SCD, and with a normal or enlarged spleen in patients with HgbSC, pathologists may wrongly dismiss bone marrow emboli as consequences of cardiopulmonary resuscitation, when those emboli might actually have been causative of fatal ACS.

Thrombotic thrombocytopenic purpura: yesterday, today, tomorrow.

Although much has been learned about the pathophysiologic process of thrombotic thrombocytopenic purpura (TTP), both diagnostically and therapeutically, since its initial description by Moschcowitz in 1924, its etiology and treatments remain, in many instances, problematic. Thrombotic thrombocytopenic purpura remains a rare entity whose etiology is usually unknown, but several drugs and infections have now been implicated in its development (i.e. Cyclosporine A, Mitomycin-C, Ticlopidine, Simvastatin, Lipitor, Plavix, FK 506, Rapamune (sirolimus), HIV). Although its treatment by plasma exchange has gained worldwide acceptance since the late 1970s, the optimal exchange media is not known, nor the volume and duration of exchange therapy, nor appropriate salvage therapy(ies). Without the benefit of randomized controlled trials, its treatment, to a large extent, remains not evidence-based but 'eminence-based', making the same mistakes with increasing confidence over an impressive number of years.

Drug-induced thrombotic thrombocytopenic purpura/hemolytic uremic syndrome: a concise review.

An extensive variety of drugs have been associated with thrombotic thrombocytopenic purpura and hemolytic uremic syndrome (TTP/HUS). Although a direct causal effect has usually not been proven, the cumulative evidence linking several drugs with TTP/HUS is strong. This paper reviews several categories of drugs including antineoplastics, immunotherapeutics and anti-platelet agents that have been reported to induce TTP/HUS. The pathogenesis of drug-induced TTP/HUS and the effectiveness of treatment regimens are also reviewed. A consensus on diagnostic criteria to accurately and consistently diagnose drug-induced TTP is needed.

Evidence-based medicine for apheresis: an ongoing challenge.

Although much has been learned about the pathophysiologic process of thrombotic thrombocytopenic purpura (TTP) since Moschcowitz's initial description in 1924, its etiology and treatments remain problematic. We treated our first patient with TTP by plasma exchange in 1975 and have now treated over 160 patients. We report our experience exchanging patients using FFP, solvent detergent (SD) and cryopoor plasma as the exchange media. Most patients experience allergic reactions, some severe, during the course of treatment. However, use of SD plasma virtually eliminates all allergic reactions. Splenectomy was a much more common treatment prior to plasma exchange, but can still be a useful treatment option for some refractory patients. Recombinant ADAMTS-13 can hopefully provide not only more useful diagnostic assays but also could provide specific and more efficacious treatment of patients with both acquired and familial forms of TTP.

Inflammatory pseudotumor of the spleen in a 6-year-old child: a clinicopathologic study.

Inflammatory pseudotumors of the spleen are extremely rare in children. To our knowledge, only 3 cases of splenic inflammatory pseudotumors have been reported. An inflammatory pseudotumor of the spleen was found incidentally during the workup of vesicoureteral reflux disease in a 6-year-old girl. The clinical, pathologic, immunophenotypic, and molecular features and the differential diagnostic features are discussed here. Splenic inflammatory pseudotumors, although rare, should be considered in the differential diagnosis of a mass lesion of the spleen in children.

Myocardial infarction/injury is relatively common at presentation of acute thrombotic thrombocytopenic purpura: the Indiana University experience.

Although widespread vascular thrombosis is common in thrombotic thrombocytopenic purpura (TTP), there have been no prospective studies on the extent of injury to specific organs. Following successful resuscitation and plasma exchange of an index patient with widespread organ dysfunction, cardiogenic shock, and elevated cardiac troponin-I levels, we prospectively studied and identified 2 more individuals (of 10 consecutive patients) with evidence of myocardial injury/infarction at presentation of acute TTP. These data suggest that cardiac troponin-I measurements should be considered during initial evaluation of all patients with acute TTP.