Amira Many

Single and Combined Prothrombotic Factors in Patients With Idiopathic Venous Thromboembolism: Prevalence and Risk Assessment

The inherited thrombophilias--deficiencies of protein C, protein S, and antithrombin III--and the prothrombotic polymorphisms factor V G1691A and factor II G20210A predispose patients toward venous thromboembolism (VTE). The aim of this study was to determine the prevalence of single and combined prothrombotic factors in patients with idiopathic VTE and to estimate the associated risks. The study group consisted of 162 patients referred for work-up of thrombophilia after documented VTE. The controls were 336 consecutively admitted patients. In all subjects factor V G1691A, factor II G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T were analyzed by specific polymerase chain reactions and restriction enzymes. Activities of antithrombin III and protein C, free protein S antigen, and lupus anticoagulant were determined in a subset of 109 patients who were not receiving oral anticoagulants. The prevalences of heterozygotes and homozygotes for factor V G1691A and factor II G20210A among patients and controls were 40.1% versus 3.9% and 18.5% versus 5.4%, respectively (P=0.0001). The prevalence of homozygotes for MTHFR C677T in patients was 22.8% and in controls, 14.3% (P=0.025). Heterozygous and homozygous factor V G1691A, factor II G20210A, and homozygous MTHFR C677T were found to be independent risk factors for VTE, with odds ratios of 16.3, 3.6, and 2.1, respectively. Two or more polymorphisms were detected in 27 of 162 patients (16.7%) and in 3 of 336 controls (0.9%). Logistic regression analysis disclosed odds ratios of 58.6 (confidence interval [CI], 22.1 to 155.2) for joint occurrence of factor V and factor II polymorphisms, of 35.0 (CI, 14.5 to 84.7) for factor V and MTHFR polymorphisms, and of 7.7 (CI, 3.0 to 19.6) for factor II and MTHFR polymorphisms. Among 109 patients in whom a complete thrombophilic work-up was performed, 74% had at least 1 underlying defect. These data indicate that in most patients referred for evaluation of thrombophilia due to idiopathic VTE, 1 or more underlying genetic predispositions were discernible. The presence of >1 of the prothrombotic polymorphisms was associated with a substantial risk of VTE.

Heredity and Coagulation Studies in Ten Families with Factor XI (Plasma Thromboplastin Antecedent) Deficiency

Rosenthal, Dreskin and Rosenthal (1953) described a familial haemorrhagic disorder due to plasma thromboplastin antecedent (PTA) deficiency. Further studies have established the properties of this factor and its action in the early phase of thromboplastin generation (Rosenthal, 1954; Rosenthal, Dreskin and Rosenthal, 1955; Ramot, Angelopoulos and Singer, 1955; Campbell, Mednikoff and Dameshek, 1957; Cavins and Wall, 1960). The mode of hereditary transmission of this deficiency has been discussed by various authors (Cavins and Wall, 1960; Campbell et al., 1957; Rosenthal et al., 1955). Recently Rapaport, Proctor, Patch and Yettra (1961), using a quantitative assay of PTA, suggested that this deficiency is transmitted by an intermediate gene, which produces major PTA deficiency in the homozygote and minor PTA deficiency in the heterozygote. In the present communication, 10 families with PTA deficiency will be described and the mode of its inheritance will be discussed.

The Effect of Cyclophosphamide Pulses on Fertility in Patients With Lupus Nephritis

ABSTRACT: The effect of cyclophosphamide pulse therapy given in relatively small doses (10 mg/kg per pulse) in 17 females with lupus nephritis has been studied. Four females developed menopause; in one transient amenorrhea occurred. No changes in menstrual cycle were noted in the other 11 females, four of whom subsequently delivered five normal babies. These data suggest the relative safety of small doses of cyclophosphamide pulse therapy on gonadal function in females under age 40 years.

Serum immunoglobulins in chronic lymphocytic leukemia.

Serum immunoglobulin levels were periodically determined in 70 CLL patients and the changes were correlated with several clinical and laboratory parameters. It was found that the IgG and IgA levels decreased significantly as the disease progressed. A low IgG concentration was found at the time of diagnosis in 18.7% and after six years in about 50% of the patients. The IgM concentration, although initially low, increased during the follow-up in 43% of the patients and in four of them a monoclonal fraction appeared in the serum. The changes in the immunoglobulins did not correlate with age, sex or initial leukocyte count. Stage 0 patients as well as untreated patients also had a decrease in their immunoglobulin levels but advanced disease stage and especially continuous chemotherapy seemed to augment the drop in the immunoglobulin levels. Neither the initial immunoglobulin levels nor the subsequent changes, absolute or relative, had a significant prognostic value.

Circulating Anticoagulant in Systemic Lupus erythematosus: Clinical Manifestations

The correlation between the presence of lupus circulating anticoagulant (LCA) and the incidence of thromboembolic phenomena was evaluated in 66 systemic lupus erythematosus (SLE) patients. Our criteria for the presence of LCA included an elevated LCA index and a prolonged recalcification time. Thirty-two patients (48%) fulfilled these criteria (group A). The incidence of thromboembolic phenomena, recurrent abortions and involvement of the nervous system was higher in group A patients than in SLE patients without LCA (group B). Moreover, 16 patients of group A who exhibited also a positive thromboplastin inhibition test associated with a markedly elevated LCA index, manifested higher incidence of severe thromboembolic phenomena. Early detection of LCA has important therapeutic implications. We suggest that the presence of LCA should be recognized as one of the criteria for the diagnosis of SLE.

Myocardial Infarction in a Young Woman With Systemic Lupus Erythematosus

We describe the case of a young woman with systemic lupus erythematosus (SLE) who suffered an acute myocardial infarction (MI). The patient was treated by corticoste roids in addition to the usual management for acute MI. The role of arteritis in produc ing the infarction is also discussed.

Primary Intestinal Lymphoma: Clinical Manifestations and Possible Effect of Environmental Factors

Lymphoma of the small intestine can occur as a late secondary manifestation of disseminated lymphoma, or far less commonly, as a primary lesion originating in the small intestine or mesenteric lymph nodes [1–6]. The latter disease can be further subdivided into two categories: a) Solitary lymphoma that occurs most commonly in the terminal ileum and is encountered more frequently in young children, and b) Diffuse or multifocal small intestinal lymphoma, occurring most commonly in proximal small intestine encountered primarily in the older age groups. In the latter entity malabsorption has been described [3–5]. The syndrome of malabsorption in small intestine lymphoma as described by EDELMAN et al. (1966), occurs only rarely in the more developed countries of the Western world [7]. These authors, reviewing the medical literature of the West, were able to find only 48 cases, of which they regarded 32 as well established and 16 as probable. On the other hand, the syndrome of malabsorption in small intestinal lymphoma is not rare among certain populations whose common denominator appears to be that they are under-privileged in terms of nutrition, hygiene and medical care [7–11]. In Israel the syndrome is relatively prevalent among Arabs and among first and second generations of Jewish immigrants from mid-eastern and North Africa countries and is virtually non exsistent among Jews of European origin [7–10]. This syndrome was also described in other Mediterranean populations as, North Africa, Italy, Spain as well as in Iran, Mexico, South America and in the African-Cape-Coloured people [11–13]. The evidence thus far would seem to suggest that predisposition to primary small intestinal lymphoma is environmentally determined. One could also speculate about the unique vulnerability of certain populations due to genetic factors or a combination of environmental and genetic influences. In this work we summarized the present day knowledge on this entity and analysed the possible effects of environmental factors on its development. The possibility of abnormalities in the lymphoreticular system and its possible effect on the disease will also be discussed.

Acute lymphoblastic leukemia subtypes in israel: The sheba medical center experience☆

During the period from 1978 to 1981, 52 patients with ALL were diagnosed and treated at the Chaim Sheba Medical Center. Using standard cell markers to subtype the blasts, 49 of the patients could be classified: 16 were found to be T-cell ALL, 10 common ALL, five null ALL, four pre-B and 14 were partially characterized as non-B, non-T. Analysis of the series revealed two distinctive features: high prevalence (30%) of T-cell ALL among both Jews and Arabs and a high proportion, two-thirds, of high risk patients due to high initial WBC counts, unfavourable age or T-cell characteristics. The minimal incidence of ALL among the Gaza Strip Arab children during the study period is 4:100,000, which is close to the incidence in the Western world. During previous years the leukemia incidence in the Gaza Strip was very low while the most common lymphatic malignancies were Burkitt tumor and other non-Hodgkin lymphomas.

Outcome of pregnancy in three patients with primaryantiphospholipid syndrome after stroke

OBJECTIVE Ischemic stroke is the most common neurological manifestation in patients with antiphospholipid syndrome (APS). Pregnancy in APS patients markedly increases the risk of thrombosis. There is no data on pregnancy outcome in patients with APS with a history of an ischemic stroke. We report our experience with three APS patients with a history of stroke who had successful pregnancies and deliveries. PATIENTS Three patients with APS and previous stroke were treated with small doses of aspirin and anticoagulants during pregnancy. RESULTS The patients remained free of attacks of cerebral ischemia during their pregnancies and at follow-up periods of 1 to 4 years. CONCLUSIONS Successful pregnancy and delivery is possible in APS patients with a history of stroke, treated with low-dose aspirin and anticoagulants. A previous episode of cerebral ischemia should not be considered an absolute contraindication for an APS patient to become pregnant.

The distribution of B and T lymphocytes in the peripheral blood of patients with Hodgkin's disease.

The distribution of thymus-dependent (T cells) and bone marrow-derived lymphocytes (B cells) was studied in 74 patients with Hodgkins disease and 33 normal controls. A T cell deficit was found in untreated patients as well as in long-term survivors in remission. Therapy slightly enhanced the T cell depletion in Hodgkins disease patients. Concomitant with this finding was slight increase of B cells.