Kojiro Yasunaga

Effects of Kami-kihi-to (Jia-Wei-Gui-Pi-Tang) on autoantibodies in patients with chronic immune thrombocytopenic purpura

We studied the effect of Kami-kihi-to (Jia-Wei-Gui-Pi-Tang) on the production of autoantibodies in ten patients with chronic immune thrombocytopenic purpura. After administration of Kami-kihi-to, platelet count was increased in seven of the ten patients (p < 0.05). Using Western blotting, we demonstrated the disappearance of autoantibody reaction with antigen in one patient. However, platelet-associated IgG was decreased in eight of ten patients (p < 0.05). Kami-kihi-to appears to promote the suppression of autoantibodies in patients with chronic immune thrombocytopenic purpura. No side effects were observed in any patient. Thus, Kami-kihi-to may be a useful and safe drug in the management of chronic immune thrombocytopenia purpura.

Statistical analysis of Glanzmann's thrombasthenia in Japan.

Kojiro Yasunaga, First Department of Internal Medicine, Kansai Medical University, 1-Fumizonocho, Moriguchi, Osaka 570 (Japan) Glanzmann’s thrombasthenia (GT) is a well-defined inherited disorder ofplatelet function [1-3]. GT has an au-tosomal recessive inheritance and is characterized by the absence of ADP-induced platelet aggregation. It is caused by a deficiency or abnormality of the membrane glycopro-tein (GP) Ilb/ΠIa complex, with bleeding occurring due to defective platelet haemostatic plug formation. We have carried out nationwide surveys of congenital platelet function disorders in Japan on four occasions (in 1976,1981, 1986 and 1991). There were 98 patients in 1976,160 in 1981,178 in 1986, and 192 in 1991. Bleeding symptoms appeared at around 3 years of age in 60% of GT patients in all four surveys. The most common symptoms were epistaxis (70.7% in 1976, 70.8% in 1981, 70.2% in 1986, and 70.4% in 1991) and pur-pura (63.9% in 1976, 62.4% in 1981, 62.7% in 1986 and 61.9% in 1991). These were followed in descending order by oral mucosal bleeding, genital bleeding, excessive bleeding after tooth extraction, haematemesis and me-laena, excessive bleeding following trauma, and haematu-ria. In all 4 surveys, laboratory studies showed that the platelet count was normal in these patients, while the bleeding time was prolonged and ADP-induced aggregation was absent or decreased by more than 90%. The most interesting results were the mortality rate and the age distribution. The mortality rate was 6.8% in 1976, being slightly higher than that for haemophilia and related disorders (4.4% of 3,193 patients in 1976). The reason for this difference may be the lack of an effective haemostatic drug for GT patients, while coagulant factor therapy can be utilized for haemophilia. The mortality rate of GT patients has slowly declined since that time, with the standardized mortality ratios for age and sex showing a similar pattern (table 1). Table 1. Changes of the mortality rate of GT patients Year Mortality rate Standardized mortality ratio

Effect of three Japanese kampo medicines on platelet activation by monoclonal anti-platelet membrane glycoprotein antibodies.

We studied the effect of three Japanese kampo medicines on platelet activation by an anti-CD9 monoclonal antibody (NNKY1-19) and an anti-human Fc gamma receptor II monoclonal antibody (NNKY3-2). Sho-saiko-to (TJ-9) and Sairei-to (TJ-114) partially suppressed platelet aggregation induced by NNKY1-19, while Juzen-taiho-to (TJ-48) suppressed aggregation induced by NNKY3-2. TJ-9 and TJ-114 also suppressed collagen-induced aggregation, but TJ-48 did not. Flow cytometry showed that the three medicines did not affect antibody binding to the platelets. Thus, all three kampo medicines suppressed platelet activation by anti-platelet glycoprotein antibodies without inhibiting antibody binding.

Follow-up of HIV Carriers by a Laboratory Method

We followed 54 HIV-1 carriers (44 asymptomatic carriers and 10 AIDS patients) by virus isolation and immunological examination and evaluated their usefulness for prognostication of the onset of symptoms. From 37 carriers (27 asymptomatic carriers and 10 symptomatic), 132 HIV-1 strains were isolated; the virus isolation rate was 60% in the asymptomatic carriers (AC) but 100% in the symptomatic. In the AC, the isolation rate was 54.5% in the group showing stable in the CD4+ level but 95.5% in the group showing a decrease in the CD4+ level. With progression of the disease, the culture time required for virus isolation was shortened, and the percentage of isolates showing infectivity to the T-cell line (MT-4 cells) increased. These findings suggest that the virus in the body is changed with progression of the disease to that showing rapid replication, T-cell tropic, and high pathogenicity. Indeed, progression of the disease was observed in all carriers in whom a highly pathogenic virus was detected; some developed the disease within 1 year, some showed temporary recovery in the CD4+ level after AZT administration followed by progression to ARC, and others showed a rapid decrease in the CD4+ level. In contrast, in carriers with only slightly pathogenic virus, the CD4+ level was maintained for a long period. These results suggest that the detection of a highly pathogenic virus is one of the most reliable marker for the prognostication of the onset of the disease. The detection of HIV-1 antigen in the plasma and a decrease in the gag antibody were also associated with the progression of the disease. However, the reliability of these markers seems to be lower than that of virus isolation.

Report on two cases having anti-Wra antibody with special reference to the background of anti-Wra production.

Here reported are two patients having anti-Wra antibody, which have been uncommon in Japan. Further, we have found 38 such cases so far reported in our country. The 40 cases in all have been examined on their backgrounds which might be related to the anti-Wra production.1) Case report: Case No. 1: A 78-year-old female, complaining of dizziness and palpitation, was found to have autoimmune hemolytic anemia.She had never received blood transfusion. Her blood group was B, CcDEe, Wr (a-). Direct antiglobulin test (DAT) using anti-IgG was positive, and the eluate from RBC reacted against all of the panel red cells, showing presence of panreactive warm-type anti-RBC autoantibody. The patients serum, even after its autoantibody was absorbed by her own RBC, still showed presence of anti-Wra.Case No. 2: A 68-year-old male had been suffering from the myelodysplastic syndrome, which thereafter transformed to myelocytic leukemia.His blood group was A, Rh (D)-positive. The screening test for unexpected anti-RBC antibodies was initially negative, which turned to positive along with DAT after frequent blood transfusions. Further laboratory tests detected panreactive warm-type anti-RBC autoantibody in the eluate from the patients RBC as well as alloimmunized anti-E and anti-Wra in his serum.2) Results obtained by the survey on the anti-Wra in Japan: In the majority of the 40 cases with anti-Wra in Japan, including our above-mentioned two, the anti-Wra seemed to be a natural antibody, while, in 3 of them, anti-Wra was coexistent with the warm-type anti-RBC autoantibody. Besides, other 2 cases seemed to be drug-induced. These findings raise interests in the etiology of anti-Wra. However, the anti-Wra itself may be clinically innocent here in Japan, because any individuals having the blood group antigen Wra have not yet been found among Japanese. In addition, if Wra-positive RBC will be hereafter more commonly included in panel red cells for screening unexpected anti-RBC antibody, anti-Wra may, probably, be more frequently detected in Japan.

PRIMARY THROMBOCYTHEMIA ASSOCIATED WITH ERYTHROMELALGIA, WITH A SPECIAL REFERENCE TO THE MECHANISM OF PAIN: REPORT OF A CASE

原発性血小板血症といわれるものには,いわゆる“thrombohemorrhagic phenomena”を呈するものと血栓形成又はそれに近似する症状を呈する場合のものとが臨床的に報告されている.血小板増加の原因はもちろん,出血や血栓形成,疼痛などの発現機序についてはほとんど解明されていないのが実情である.最近著者等は78才,女性で典型的erythromelalgiaを伴つて発症し,何ら基礎的疾患と思われるものなく,持続する血小板増加と趾疼痛を来たした原発性血小板血症の1例を経験した.検査上,末梢血中血小板は100×104/μI以上の増加を認めるが,その他の成績に著変なく凝固,線溶系の検査もほぼ正常であつた.また骨髄塗抹,生検所見では従来本症に特徴的と言われる巨核球系を中心とした過形成がなく,この点からも自験例は希な症例と言える.しかも趾疼痛がaspirin l回の投与により7～10日間は完全に消失した事実から疼痛の発現と血小板機能との関係に検討を加えた.すなわちaspirinは血小板機能発現に重要なprostaglandin (PG) endoperoxidesの生成酵素であるcyclooxygenaseを非可逆的に阻害し血小板凝集阻止を行なう事から, PG eodoperoxidesに由来すると考えられるmalondialdehyde (MDA)を指標としてaspirin投与後のPG endoperoxides生成や,血小板凝集能を検索したところ,疼痛発現にはこれらの血小板機能が密接に関与している事が明らかとなつた.また治療では欧米で盛んに用いられて来た32Pは使用せず, busulfanpによる化学療法を試みた結果,血小板数の減少とともに疼痛も消失し満足すべき治療効果が認められた.

Integrated analysis of hemorrhagic-thrombotic tendency

Abstract To diagnose hemorrhagic, thrombotic, and hemorrhagic-thrombotic tendencies respectively, the Hemorrhagogram, Thrombogram, and Hemorrhago-thrombogram were devised. In the Hemorrhagogram, the tests on platelets and the vessel wall, namely, platelet count, bleeding time, clot retraction, and capillary fragility, the tests on coagulation, namely, clotting time, activated partial thromboplastin time (PTT), prothrombin time, and r and k values of thrombelastogram (TEG), and the tests on fibrinolysis, namely, fibrinogen and euglobulin lysis time (ELT) were performed. We prepared the Thrombogram taking fibrinogen and heparin resistance as indicators for coagulation, platelet adhesiveness or platelet aggregation for platelets, plasma clot lysis time (PLT) and ELT for fibrinolysis, and blood viscosity and the TEG-ma value as overall indications. In the Hemorrhago-thrombogram, a series of fifteen tests on blood platelets, coagulation and fibrinolysis, namely, blood viscosity, platelet count, bleeding time, clot retraction, prothrombin consumption, platelet factor 3, platelet adhesiveness, platelet aggregation induced by ADP, TEG, heparin resistance, prothrombin time, PTT, fibrinogen, PLT and ELT, was performed on each blood sample. These diagrams not only gave us an immediate picture of the condition of the disease, but also confirmed the need to make an overall judgment of the essential factors involved in hemorrhagic and/or thrombotic diseases. This kind of integrated analysis is thought to provide a useful indicator for the diagnosis and treatment of these diseases.