Hamid Al-Mondhiry

Natural History of Human Immunodeficiency Virus Infections in Hemophiliacs: Effects of T-Cell Subsets, Platelet Counts, and Age

Serial T-cell subsets and platelet counts were determined in a cohort of 84 hemophiliacs in whom time of seroconversion for human immunodeficiency virus (HIV) antibody could be ascertained. An abrupt decrease in the number of T-helper (T4) cells was seen in 9 patients 12 to 24 months before the acquired immunodeficiency syndrome (AIDS) was diagnosed (p = 0.0007 compared with those who did not develop AIDS). Thrombocytopenia also was associated with an increased risk for AIDS (p = 0.02), as was older age at the time of seroconversion (p = 0.03). Ten patients developed AIDS at 24 to 95 months after seroconversion, for a cumulative incidence (+/- SE) of 18.0% +/- 7.1% at 6 years. Hemophiliacs who had T4 cell counts of less than 200 cells/microL had a 50% +/- 16% cumulative incidence of AIDS within 2 years, indicating that decreasing or very low T4 cell counts have predictive value for the development of AIDS. Furthermore, the data suggest that thrombocytopenia and older age may be markers for a cofactor that increases the risk for AIDS in hemophiliacs.

Idiopathic thrombocytopenic purpura in lymphoma

Five patients with idiopathic thrombocytopenic purpura (ITP) associated with malignant lymphoma are presented, and twelve other cases reported in the literature are reviewed. Thirteen patients (76%) had Hodgkins disease; two had diffuse histiocytic, one, diffuse mixed lymphoma. Idiopathic thrombocytopenic purpura presented as the sole clinical manifestation of initial or recurrent lymphoma in 10 of 15 cases (67%). The spleen was not palpable even in patients who showed involvement with lymphoma at splenectomy. Three patients were asplenic at the onset of idiopathic thrombocytopenic purpura. Successful therapy of the thrombocytopenia correlated with effective control of the underlying lymphoma. Splenectomy gave favorable results in 9 of 10 cases (90%) and uncovered occult lymphoma in five patients. Chemotherapeutic drugs were successful in seven of 12 trials (58%) and only when the underlying disease was also controlled. The overall prognosis was related to the status of the lymphoma and was not altered by the occurrence of the idiopathic thrombocytopenic purpura.

Neurologic manifestations of intravascular coagulation in patients with cancer. A clinicopathologic analysis of 12 cases.

Among 1,459 autopsied patients with cancer, 12 had multifocal infarcts of the brain that appeared to be caused by intravascular coagulation. Most of these patients were women with leukemia or lymphoma, and all had a clinical course in which neurologic signs and symptoms were prominent. All had evidence of generalized brain disease (delirium and stupor or coma), and several also had focal brain disease (focal seizures, hemiparesis). All patients had laboratory evidence of coagulation abnormalities, although these were often not severe when neurologic symptoms began. Pathologically, there were multifocal hemorrhagic or ischemic infarcts in the distribution of several cerebral vessels, without a systemic source for cerebral emboli. Fibrin thrombi were identified in cerebral vessels and in vessels of several other organs. The clinical findings fit the pathologic picture, and in most instances the correct diagnosis might have been made earlier had it been considered.

Acute leukemia in Hodgkin's disease

Three cases of Hodgkins disease terminating in acute leukemia are described and the literature reviewed. All 3 patients were diagnosed within the past year and were noted among 1095 patients with Hodgkins disease seen during the last 15 years at Memorial Hospital in New York. The interval from the diagnosis of Hodgkins disease to the documentation of leukemia was 8 years, 10 months, and 7 years in the 3 patients, respectively. Two patients developed myelomonocytic leukemia, and the 3rd monocytic leukemia. All 3 patients died within 6 months from the diagnosis of leukemia with no significant response to treatment. Two patients had radiotherapy and chemotherapy prior to the diagnosis of leukemia, and a 3rd patient had only chemotherapy for their Hodgkins disease. Radiotherapy and chemotherapy as possible leukemogens are considered.

On the Mechanism of Platelet Function Inhibition by Acetylsalicylic Acid

Summary Aspirin produces alteration of platelet function characterized by loss of secondary aggregation in response to ADP or epinephrine, and inhibition of aggregation by collagen. In addition, platelet factor 3 release by these reagents is reduced. A similar platelet lesion was produced by an acetylating agent, acetic anhydride, supporting earlier concepts that aspirin activity against platelets may be a consequence of acetylation. An attempt to identify specific acetylation of platelets with acetyl-1-14C salicylic acid was unsuccessful. Although platelet uptake of the label was demonstrated, metabolic incorporation of acetate could not be excluded.

Successful use of argatroban during the third trimester of pregnancy: case report and review of the literature.

Direct thrombin inhibitors are commonly used anticoagulants in patients with known or suspected heparin‐induced thrombocytopenia (HIT). All three direct thrombin inhibitors available in the United States—argatroban, bivalirudin, and lepirudin—are pregnancy category B drugs based on animal studies, but little data are available on the safety of these agents during human pregnancy. Whereas several case reports support the safe use of lepirudin, only one case report has been published with argatroban and none with bivalirudin. We describe a 26‐year‐old pregnant woman with portal vein thrombosis and thrombocytopenia treated with argatroban for possible HIT during her last trimester. An argatroban infusion was started at 2 μg/kg/minute during her 33rd week of pregnancy, with the dosage titrated based on the activated partial thromboplastin time; infusion rates ranged from 2–8 μg/kg/minute. Treatment continued until her 39th week of pregnancy, when labor was induced. Argatroban therapy was discontinued 7 hours before epidural anesthesia. The patient successfully delivered a healthy male newborn, devoid of any known adverse effects from argatroban. The infant was found to have a small ventricular septal defect and patent foramen ovale at birth, but it is unlikely that these were caused by argatroban since organogenesis occurs in the first trimester. Even though the cause of this patients thrombocytopenia was later determined to be idiopathic thrombocytopenic purpura, this is an important case that adds to the literature on use of argatroban during pregnancy.

Alpha heavy chain disease (report of 18 cases from Iraq).

The clinical and pathological features of 18 new patients with alpha heavy chain disease seen at two referral centres in Baghdad, Iraq, are described. The series included 14 males and four females ranging in age from 14 to 47 years. Almost all patients presented because of long-standing abdominal pain and diarrhoea. The tissue diagnosis and extent of the disease were established at laparotomy in most patients. Peroral jejunal biospy was used in a number of patients, mainly for follow-up. The serological abnormality was confirmed by immunoselection technique. Most of the patients had extensive thickening of the bowel wall and/or tumour masses of the small intestine and mesenteric nodes. Histopathological sections showed muscularis. Preliminary results of the treatment, including two long remissions, are reported. In general, our observations agree with those made by other authors, mostly from the Middle East and Africa. We believe that a high index of clinical suspicion, routine use of the immunoselection, and recognition of the early pathological changes may hopefully lead to the detection of more cases before the frank neoplastic phase of the disease.

Clinical and pathologic subtypes of primary intestinal lymphoma. Experience with 132 patients over a 14-year period.

Primary lymphomas of the small intestine (PIL) show definite racial and geographic distribution. Clinical and laboratory data on 132 patients with PIL treated and followed up over a 14‐year period in Baghdad, Iraq, are presented. Based on the pattern of involvement of the bowel and the histopathologic appearance of the tumor, the patients can be divided into three main groups. Ninety‐seven patients had diffuse lymphoplasmacytic infiltration affecting large segments of the upper bowel. Abdominal pain, anorexia, weight loss, diarrhea, malabsorption, and clubbing of the fingers are the most common clinical findings. The barium appearance of the small intestine and peroral jejunal biopsy specimens are abnormal in nearly all cases. This clincopathologic entity has been referred to in the literature as Mediterranean lymphoma (ML). Ten of 34 patients tested had free alpha‐heavy chain in the serum. Twenty‐three cases had other “Western” variants of lymphoma (18 lymphocytic and 5 plasmacytic). The lesions were localized, occurring most frequently in the lower ileum or ileocecal area. The most common presentation was intestinal obstruction. Twelve children had Burkitts lymphoma (BL), presenting most commonly with abdominal masses and/or intestinal obstruction. These patients responded poorly to cyclophosphamide, and the disease disseminated early and extensively. None of the patients with the localized lymphomas or BL had free alpha chain in the serum.

Association of a chromosomal abnormality with lymphocytes having both T and B markers in a patient with lymphoproliferative disease.

The lymphocytes of a patient with leukemic lymphosarcoma were found to have an unusual surface phenotype in that they bound both sheep erythrocytes (a T cell marker) and complement-coated erythrocytes (a B cell marker) but lacked other B cell surface characteristics. Marker chromosomes were present in these cells, but not in other, phenotypically normal cells from the same patient. This case may provide a clue to the chromosomal origin of some lymphocyte surface markers in man.

Congenital afibrinogenemia and splenic rupture.

<0.05). These data show that there was improvement in all measured variables following reduction in PCV to 0.5, and that this continued as the red cell mass was further decreased. Thus, we conclude that in this group of patients with normal cardiorespiratory function, a reduction of PCV to 0.40 L-L-r results in optimal function. The situation in patients with hypoxic lung or cyanotic congenital heart disease may well be different because oxygen transport could be deleteriously impaired when the hemoglobin concentration is reduced. Perloff et al