Recently, we described a platelet antibody against a putative collagen receptor (P62), which was found in a patient with idiopathic thrombocytopenic purpura (ITP) (Blood 69:1712). We now report a deficiency of the P62 receptor in a young man whose platelets showed defective collagen-induced platelet aggregation. He had a mild bleeding tendency and slight thrombocytopenia. The results of coagulation and fibrinolysis studies were normal. The patient's platelets were partially unresponsive to collagen, although aggregation in response to ADP, thrombin, ristocetin, and calcium ionophore (A23187) was almost normal. Adhesion of his platelets to bovine collagen was markedly reduced. Addition of collagen caused no synthesis of thromboxane (TX)B2 in platelet rich plasma (PRP) from this patient. Furthermore, collagen produced no rise of cytosolic free calcium ([Ca2+]i) in fura2-loaded platelets. In contrast, thrombin caused TXB2 formation and an increase of [Ca2+]i in his platelets. These results suggest defective interaction between the platelets and collagen. The IgG from the ITP-patient induced irreversible aggregation in normal PRP, but caused no aggregation of the young man's platelets. Immunoblot studies showed that normal platelets had antigens with a molecular weight of 62 KDa under reducing conditions and of 57 KDa under nonreducing conditions. In contrast, the young man's platelets had no P62 band, although GPIa/IIa and thrombospondin were normally present. These results indicate that impaired collagen-induced aggregation in the patient's platelets was due to a deficiency of P62 and confirm that P62 may play a crucial role as a collagen receptor in platelet activation.

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A novel compound heterozygous mutation of 317 CGC-->TGC with 142 GCT-->ACT in human red cell band 4.2 deficiency is described. A proband and his son suffered from compensated haemolysis with nearly complete deficiency of red cell band 4.2. Their red cell morphology exhibited microspherocytosis resembling classic hereditary spherocytosis (HS). Sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS-PAGE) showed band 4.2 to be nearly missing (< 1% of normal controls) with the presence of 74 kD and 72 kD isoforms in trace amounts. Other family members (daughters older and younger than the son) exhibited nearly normal amounts of 72kD as a wild form of band 4.2 on SDS-PAGE with the presence of the 74kD isoform in a trace amount. The proband and his son demonstrated two compound heterozygous mutations in trans: i.e. nucleotide (nt) 949 CGC-->TGC (codon 317 Arg-->Cys) in exon 7 and nt 424 GCT--ACT (codon 142 Ala-->Thr) in exon 3 of the band 4.2 gene. The two daughters demonstrated only the mutation of nt 949 CGC-->TGC in exon 7 in heterozygous states, but no 142 mutation. Therefore the proband and his son were compound heterozygotes of these two mutations in trans. It is interesting to note that the 74 kD isoform of band 4.2 protein existed in a trace amount in the two daughters in spite of the absence of the 142 Ala-->Thr mutation. In addition, even in the presence of the 142 mutation in one allele in the proband and his son, their red cell morphology demonstrated classic HS with microspherocytosis, although a homozygous state of the 142 mutation known as the Nippon type of band 4.2 deficiency exhibits ovalostomatocytosis.

We describe two patients with non-Hodgkin’s lymphoma (NHL) who suffered cytomegalovirus (CMV)-related small intestinal perforations during the course of chemotherapy. Surgical specimens from both patients revealed his-tologic evidence of occlusive vasculitis and tissue destruction caused by CMV-affected cells in the submucosa and muscular walls, that may have played an important role in the pathogenesis of these perforations. Although such intestinal perforations are rare complications in NHL patients, CMV infection should be recognized as a primary etiological factor in acute abdominal crises when treating NHL patients with pharmaceutical agents including steroids. Emergency surgery and the anti-CMV agent, ganciclovir, would improve the prognoses of such patients.

A 61-year-old man with Philadelphia chromosome-positive chronic myelogenous leukemia developed megakaryoblastic leukemia. In the blast phase, his blast cells showed undifferentiated megakaryoblastic characteristics with no alpha-granules or demarcation membranes but with detectable platelet peroxidase (PPO) activity and surface glycoprotein (GP) IIb/IIIa. The patient has remained reasonably well for at least 12 months after blastic crisis, and 6-mercaptopurine alone has been effective in controlling leukocytosis and megakaryoblast proliferation. The expression of mRNA for platelet-specific proteins, such as GPIIb and platelet factor 4 (PF4), was studied in the patient's blast cells by the Northern blot analysis. Both GPIIb and PF4 mRNA were detected in the blast cells. Cytoplasmic maturation occurs later than the synthesis of the surface GP during megakaryocyte maturation. Therefore, PF4 mRNA expression should be a marker of mature megakaryoblasts. The PF4 mRNA expression in megakaryoblastic leukemia may indicate that a patient will have long survival and a good response to chemotherapy.