D-dimer in the early diagnosis of thromboembolic disease in acute spinal injuries.

The role of monitoring plasma levels of D-dimer (XDP) as a diagnostic aid for thromboembolic disease was investigated in 267 patients admitted for acute care to the Prince Henry Hospital Spinal Unit. Elevated plasma XDP levels were found in 103 patients (39%) and a diagnosis of thromboembolic disease was made in 33. Thromboembolic disease was not found in patients whose XDP levels remained normal.

First and second complete remissions in a HIV positive patient following remission induction therapy for acute non-lymphoblastic leukaemia.

A small number of patients positive for the human immunodeficiency virus (HIV) have been reported as developing acute non-lymphoblastic leukaemia (ANLL) and none has achieved remission despite attempts at treatment. We report on a 34-year-old HIV positive heterosexual intravenous drug user who presented with ANLL (FAB classification M5, Monoblastic) and entered remission following one cycle of cytosine arabinoside and daunorubicin according to the 7-3 protocol of the Australian Leukaemia Study Group (ALSG). This was followed by consolidation of 5-2 as per ALSG and one cycle of maintenance with low dose cytosine arabinoside. Ten months after remission, he relapsed but achieved a second remission with the ALSG 7-3-7 protocol (7-3 plus etoposide) followed by consolidation with 5-2-5. He remained HIV positive but showed little progression towards the acquired immunodeficiency syndrome despite the intense immunosuppression. The duration of his second remission was five months. The patient died of septicaemia during the third attempt at remission induction 18 months after diagnosis. We conclude that HIV seropositivity is not an absolute contraindication to aggressive chemotherapy in those patients who develop ANLL.

The use of a low molecular weight heparinoid (Org 10172) for extracorporeal procedures in patients with heparin dependent thrombocytopenia and thrombosis.

We report two cases of heparin induced thrombocytopenia (HIT), in patients who required anticoagulation for extracorporeal procedures (haemodialysis and cardiopulmonary bypass) one associated with recurrent thrombosis of the artificial circuits. Resolution of thrombocytopenia and successful anticoagulation were achieved using a low molecular weight heparinoid (LMWH) Org 10172. Anticoagulation was monitored using estimations of plasma anti-factor Xa activity. These cases demonstrate that LMWH provides safe and effective anticoagulation in patients in whom unfractionated heparin has caused HIT.

Oral idarubicin as single-agent treatment of acute nonlymphocytic leukemia in poor-risk patients.

Oral idarubicin was given as single-agent treatment of acute nonlymphocytic leukemia in 18 poor-risk patients. They comprised nine previously untreated elderly patients, age range 69-86, and nine relapsed pretreated patients, age range 41-76. Overall, two patients achieved complete remission (including one with preceding refractory anemia with excess of blasts) and seven achieved partial responses. Dose-limiting toxic effects were diarrhea and sepsis. In this limited study, oral idarubicin at a dose of 20-25 mg/m2/day X 3 was a well-tolerated drug with potent antileukemic effects. The oral formulation deserves more widespread evaluation.

Response of refractory anemia to low-dose cytosine arabinoside.

Two elderly patients with transfusion-dependent refractory anemia due to myelodysplastic syndromes were treated with a course of low-dose subcutaneous cytosine arabinoside in an attempt to reduce their transfusion requirements. Following treatment, they required no transfusions for over six months. The treatment was well tolerated, but was associated with initial myelosuppression.

Splenectomy for massive splenomegaly.

The technique, and short and long term results, of splenectomy for massive splenomegaly are presented. The latter was defined as a spleen weighing in excess of 1.5 kg. Thirty-five of the 38 patients had a serious haematological disorder as the indication for the operation, usually non-Hodgkin's lymphoma or myelofibrosis. All operations were carried out through abdominal incisions. Accessible splenic attachments were divided, and the splenic artery was ligated in continuity, prior to posterior mobilization. Two patients (5.3%) died as a result of the operation, both deaths being due to sepsis. Septic and thrombo-embolic complications were common, and occurred both early and late after the operation. Overall, eight of the 12 deaths during the first postoperative year were due to the primary disease, whereas all of the five deaths after that time were due to causes other than the primary disease. Twenty-four patients lived at least 1 year, and 10 patients are alive for more than 5 years.

Qualitative platelet defect in a case of heparin-induced thrombocytopenia.

A qualitative platelet defect was demonstrated in a patient with heparin-induced thrombocytopenia. His platelets showed impaired aggregation to collagen and arachidonate and absent second wave aggregation to adenosine diphosphate and epinephrine but normal response to ristocetin. These aggregation abnormalities were similar to those reported in idiopathic thrombocytopenia and systemic lupus erythematosus. This platelet function defect may contribute to haemorrhagic complications which appear to be common in heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia: effect of heparin platelet antibody on platelets.

The plasma of two patients with heparin-induced thrombocytopenia has been shown to cause platelet aggregation in the presence of heparin. The platelet aggregating factor was isolated in the IgG reaction of the patients' sera suggesting that it was an antibody. This heparin anti-platelet antibody (HAP-Ab) induced platelet aggregation and release but did not cause platelet lysis, although it fixed complement. Platelet aggregation was inhibited by EDTA and by inactivation of complement. There was a significant production of malondialdehyde (MDA) and thromboxane B2 (TXB2) implying a role of the prostaglandin synthesis pathway in HAP-Ab induced aggregation. ADP-release also appeared to be involved as apyrase blocked aggregation while hirudin, a thrombin inhibitor, had no effect. The thrombotic complications that have recently been reported in patients with heparin-induced thrombocytopenia may be explained by some effects of HAP-Ab on platelets, namely: the antibody mediated platelet factor 3 release, prostaglandin endoperoxides and thromboxane A2 (TXA2) production and platelet aggregation in vivo. These HAP-Ab mediated effects could be inhibited by anti-platelet drugs such as aspirin, indomethacin and dipyridamole and thus may have therapeutic implications.

The Lewis system and secretor status in autoimmune hemolytic anemia complicating infectious mononucleosis.

Two patients with acute infectious mononucleosis and associated immune hemolysis were found to be Le(a-b-). One of them had anti-Leb antibodies during the acute phase of the disease, which disappeared during convalescence. Two other patients with previous infectious mononucleosis and hemolysis were found to be Le(a-b-) and Le(a+b-) respectively. Of the four patients, three were nonsecretors and the fourth likely to be so. The Lewis status of these four patients varies significantly from that of other patients with uncomplicated infectious mononucleosis and from the known distribution of the Lewis type in the Caucasian population. The findings suggest that the Lewis status of the patient is important in the development of hemolysis in infectious mononucleosis.

Family study on the kindred of an adenosine deaminase deficient child with severe combined immunodeficiency.

A study was performed on the family of a child with severe combined immunodeficiency and deficiency of the purine salvage pathway enzyme, adenosine deaminase (ADA). Sixteen relatives over three generations were studied. Erythrocyte ADA levels clearly indicated the heterozygous status of five members. A sixth member, whose erythrocyte ADA level of 48 nmol/hr/ml Hb was within two standard deviations (32) of the mean (76) was shown by ADA determination on platelets to be clearly heterozygous. Similarly, consideration of ADA data of either serum, platelets or lymphocytes only, would have failed to identify all heterozygotes. The survey shows that the identification of phenotype by the indirect means of enzyme level determination is enhanced by the simultaneous study of several tissues.

IgA deficiency, superior mediastinal tumour with unusual clinical manifestations.

The clinical course of a 17-year-old man with selective IgA deficiency and anaplastic carcinoma in the superior mediastinum is described. High swinging fevers, neutrophil leucocytosis reaching 60 x 10(9)/l, polyarthralgia and skin vasodilatation were unusual manifestations of the tumour. Marked tissue reactions in the neck and polyserositis occurred with a neutrophil granulocyte tissue reaction and progressed to fibrosis. Circulating immune complexes were present and IgE levels were grossly raised. It was not established whether the unusual clinical manifestations were due solely to the tumour or were an abnormal response of an IgA-deficient host. Review of the literature of malignancy in selective IgA deficiency casts doubt upon an increased incidence of neoplasm in this immune deficiency.

The association of haemopoietic dysplasia (pre-leukaemia) and abnormal cell clone with connective tissue disease.

A 68-year-old man with haemotological features consistent with haemopoietic dysplasia (pre-leukaemia) and an abnormal cell clone in the marrow, 46, XY, -18, +t(13;18) (q11;123), developed acute connective tissue disease characterised by vasculitis, dermal changes, marked muscular weakness and serological features suggesting an auto-immune disturbance. Although four other cases of haemopoietic dysplasia ("pre-leukaemia") with unusual connective tissue disease had been reported since the recognition of haemopoietic dysplasia as a distinct entity, a definite association between these two disease states still awaits confirmation by further reports and investigations.

In vitro platelet abnormality in adenosine deaminase deficiency and severe combined immunodeficiency.

The platelets of an infant with severe combined immune deficiency and adenosine deaminase deficiency showed markedly diminished responses to ADP-induced aggregation in vitro. This abnormality was corrected by the addition of purified adenosine deaminase in vitro. Exogenous adenosine added to platelet-rich plasma caused markedly prolonged inhibition of ADP-induced aggregation. This was shown by isotopic studies to be due to slow clearance of adenosine and hence persistence of this nucleoside. Direct assay for adenosine deaminiase in plasma and platelet lysates of the patient confirmed the very low activity of this enzyme. Raised cAMP levels were demonstrated in his platelets. The deranged adenosine metabolism and raised cAMP in the platelets of this child with severe combined immunodeficiency may explain the altered response to ADP. Despite the in vitro platelet aggregation abnormality, the patient had no clinical evidence of impaired hemostasis.

Interpretation of serum and red cell folate results. A comparison of microbiological and radioisotopic methods.

Serum folate and red blood cell folate levels were measured in 167 patients using a microbiological method (Lactobacillus casei) and a commercial 125I radioassay kit. The results of the two methods were compared and related to the clinical findings to see which method more truly reflected the physiological folate status of the patient. There was a good linear correlation between the methods for both serum folate and red cell folate over the whole range encountered and the mean results obtained with each method were nearly identical. Both methods seemed to perform equally well in distinguishing low serum folate levels, but when the red cell folate results were compared to the clinical and other laboratory findings, the radioassay more closely related to the folate status of the patient. The study again emphasized the high number of low serum folate levels found in hospital patients and the importance of measuring the red cell folate.

The effect of ADP, calcium and some inhibitors of platelet aggregation on protein phosphokinases from human blood platelets.

A protein phosphokinase (ATP: protein phosphotransferase EC 2.7.1.37) which is stimulated by 3',5'-cyclic adenosine monophosphate (cyclic AMP) has been partially purified from both the cytoplasmic and membrane fractions of human platelets. The kinetics of both enzymes preparations are similar in respect to cyclic AMP, ATP, ADP and AMP. 5-10-minus 7 M cyclic AMP stimulated both preparations by approximately 100%. Both ADP and AMP at a concentration of 5-10-minus 5 M inhibited protein phosphokinase activity of the soluble and membrane preparation by between 50% and 70%. The response of the two enzyme preparations to calcium differed. 10 mM Ca-2+ inhibited soluble protein phosphokinase activity approximately 80% both in the presence and absence of 5-10 minus 7 M cyclic AMP whereas the same concentrations of Ca-2+ inhibited the membrane-bound enzyme by approximately 60% in the presence of 5-10-minus 7 M cyclic AMP and 40% in the absence of cyclic AMP. This observation may be of importance in understanding the mechanism of platelet aggregation.