[The HITT syndrome: heparin-induced thrombocytopenia and thrombosis as a cause of paradoxically occurring thromboembolisms]. / Het HITT-syndroom: door heparine geïnduceerde trombocytopenie en trombose, als oorzaak van paradoxaal optredende trombo-embolieën.

Heparin since the early sixties has played an important part in prevention and treatment of thromboembolic processes. It has hardly any side effects like allergic reactions but haemorrhage is seen more frequently. A less well-known complication is so-called heparin-induced thrombocytopenia and thrombosis (HITT). There are two different forms: a mild thrombocytopenia, characterised by a decrease in platelet count to 100-150 x 10(9)/l. This form causes no clinical symptoms. The more severe form occurs between the 7th and the 11th day after heparin administration and is characterised by paradoxically occurring thromboembolic complications. This syndrome results from formation of an antigen-antibody complex. If heparin has been administered in the past patients may develop this severe form at the moment of renewed administration. In our hospital during the past 8 years we observed 9 patients with the HITT syndrome presenting with thromboembolic complications. A thrombocyte aggregation test is diagnostically useful. Heparin-free plasma of the patient is mixed with donor thrombocytes, and heparin is added; in the HITT syndrome aggregation occurs. The main therapy is stopping the heparin administration and giving antiaggregants such as dextrans.

Including social factors in the analysis of reminiscence in elderly individuals.

Developmental psychologists have studied reminiscence in elderly individuals using widely varied conceptions of adult development. Determinist psychologists conceived of reminiscent behavior in elderly individuals as constituting the last phase in normal development. Contextualist psychologists have pointed to the historical and cultural relativity of adult development, and highlighted the variation in elderly persons with respect to reminiscent behavior. However, they do not fully acknowledge the role the environment plays in establishing reminiscent behavior in elderly people. Therefore, sociological life course theory should be included in the analyses and interpretation of this behavior.

Antimuscle and antiacetylcholine receptor antibodies in myasthenia gravis.

The sera of 134 patients were examined for antimuscle antibodies by immunofluorescence (IF). These derived from 77 myasthenics, 30 myasthenics with thymoma, 6 patients with thymoma and no clinical evidence of myasthenia, and 21 patients with other autoimmune or neuromuscular diseases. Three separate patterns of antimuscle antibodies could be identified in the myasthenic sera by examination of the relaxed glycerinated myofibrils by both IF and phase-contrast optics: A-band (9 with thymoma, 1 without), I-band (11 with thymoma, 17 without), and a mixed A plus I pattern (5 with thymoma, 3 without). Seventy-seven myasthenic serum samples (24 with thymoma, 53 without) were available for evaluation of antibodies to acetylcholine receptor (anti-AChR) by radioimmunoassay. Ninety-one percent reacted with crude human receptor extract and 80% with receptor extracted from denervated rat muscle. There was no correlation between the titers of anti-AChR and the presence or staining patterns of antimuscle antibodies, but patients without anti-AChR did not have antimuscle antibodies. Myasthenics with thymoma had the highest prevalence of anti-AChR (23/24) and of antimuscle antibodies (25/30), and 15 of the 20 positives stained A-bands alone or with I-band, as compared to 4 of 21 positive reactions in those without tumor. Immunoabsorption, which removed or significantly reduced anti-AChR, did not alter antimuscle reactivity. The discrepancies between anti-AChR levels and the presence and types of antimuscle antibodies suggest that these are independent autoantibodies. Current theories of immunopathogenesis implicate altered thymic antigens or a major breakdown in immune regulation, either of which could explain their production.

Platelet--von Willebrand factor interactions in type IIB von Willebrand's disease.

Type IIB von Willebrand's disease (vWD) is a distinct form of this disorder in which the largest multimers of the von Willebrand factor (vWF) are lacking in plasma but present in platelets. When the vasopressin analogue, 1-deamino-8-D-arginine vasopressin (DDAVP), is given to patients with type IIB vWD, an abnormal vWF is released to plasma. This vWF causes thrombocytopenia in vivo and platelet aggregation in vitro. Aggregation occurs in the plasma milieu and thus at physiological fibrinogen concentration. In this study we demonstrate that IIB post-DDAVP vWF aggregated only metabolically active platelets. The platelet aggregation was completely inhibited by EDTA and PGE1, and either inhibited or greatly weakened by ASA, demonstrating the role of divalent cations and thromboxane A2 formation. In spite of inhibiting platelet aggregation, EDTA, PGE1 and ASA did not prevent platelet binding of IIB post-DDAVP vWF. An antiserum against GP Ib made normal platelets less responsive to the IIB vWF although neither platelet aggregation nor vWF binding were completely prevented. The aggregation was fibrinogen-dependent and platelets from patients with Glanzmann's thrombasthenia were unresponsive. The studies provide evidence that IIB post-DDAVP vWF is bound to unstimulated platelets and that the interaction between vWF and platelets in type IIB vWD is different from ristocetin-induced as well as thrombin- and epinephrine-induced binding to platelets of normal vWF.

Design, findings and five-year follow-up of preventive medical lipid intervention clinic in Malmö.

In a separate lipid intervention clinic integrated within the framework of a multiphasic preventive medical population program in Malmö, 401 of 2431 screening attenders in a male birth-year cohort born in 1927 and 1928 had elevated values of triglyceride and/or cholesterol. Hypertriglyceridemia was more than three times as frequent as hypercholesterolemia. Of these attenders 20% had normal values at the second control, 5% did not attend the second test and 92 (31.2%) of the remaining were referred to other clinics because of other high risk factors. Thus, 209 (8.6% of the screening attenders) males born in 1927 and 1928 attended the lipid clinic for isolated hyperlipidemia. Disregarding a 5-year drop-out frequency of 13 sections, a significant reduction in the lipids was obtained during the follow-up period in those remaining in treatment. This study demonstrates the feasibility in taking care of hyperlipidemic individuals after a screening detection program. Detection and treatment of hyperlipidemia should of course also be initiated in the individual case in ordinary medical practice.

The use of monoclonal antibodies in measuring factor VIII/von Willebrand factor.

Here we report the production of four different monoclonal antibodies against factor VIII/von Willebrand factor (F VIII/vWF) and the use of these antibodies in immunoradiometric assay (IRMA), crossed immunoelectrophoresis (CIE) and multimeric sizing (MS) for analysing the various types of von Willebrand's disease. None of the antibodies inactivated factor VIII coagulant activity and one (R1) of them partly inhibited the ristocetin co-factor activity. One monoclonal antibody (R2) was radiolabelled and compared with 125I rabbit affinity purified antibody against F VIII/vWF. The two IRMA techniques gave similar results in 26 normals and 22 samples representing all variants of von Willebrand's disease. This monoclonal antibody could also be used in multimeric sizing and not only produced patterns identical to those obtained with the rabbit affinity purified antibody, but also gave better resolution. Further advantages of using monoclonal antibodies in these tests are: practically unlimited access to the same specific antibody, time-consuming affinity purification of the rabbit antibody can be avoided and the overall use of radioactivity reduced. This study demonstrates that one (R2) of the four monoclonal antibodies is suitable for routine analysis of F VIII/vWF and the use of this antibody simplifies the laboratory work in classifying von Willebrand's disease.

The interaction between factor VIII clotting antigen and phospholipids in genetic variants of hemophilia and von Willebrand's disease.

The interaction of factor VIII with phospholipids was investigated in 11 patients with mild and moderate hemophilia A, 7 patients with von Willebrand's disease and in 10 healthy people as controls. The addition of phospholipid vesicles containing phosphatidylserine and phosphatidylethanolamine to normal plasma and that of patients with von Willebrand's disease resulted in the loss of almost two thirds of the factor VIII clotting antigen (VIII:CAg) measurable by IRMA. Defective interaction of phospholipids with VIII:CAg was noted in some genetic variants of mild and moderate hemophilia A. Thus four of the five families tested showed decreased binding of VIII:CAg to phospholipids. One of the families tested belonged to a genetic variant with much more VIII:CAg than VIII:C, and it was in members of this family that the binding capacity was most reduced. The most probable explanations for the defective interaction with phospholipids is that molecular defects of VIII:CAg result in either decreased binding to phospholipids or might lead to a stronger binding between VIII:CAg and the von Willebrand factor (VIIIR:Ag) in the factor VIII complex and thereby preventing the normal separation of the complex.

Peripheral atherosclerosis in patients with myocardial infarction.

In 260 patients with myocardial infarction the systolic blood pressure gradient from arm to big toe was used as an indirect measure of the degree of generalized atherosclerosis. Arterial insufficiency was found in 12 per cent of the men and in 17 per cent of the women studied. The two year mortality was 19 per cent in males with arterial insufficiency as against 6 per cent in males without arterial insufficiency. This difference increased with longer (56-82 months) follow-up. The number of women was smaller but the results were similar. The present study does not support the theory that most patients with myocardial infarction have generalized atherosclerosis. Indeed, this seems to be the case in only a small fraction of such patients, thus supporting the idea that other mechanisms are also important in the etiology of myocardial infarction.

Complement-fixing antiperipheral nerve myelin antibodies in patients with inflammatory polyneuritis and with polyneuropathy and paraproteinemia.

Serum from patients with peripheral neuropathies was tested for antiperipheral nerve myelin antibodies by complement fixation. Antibody activity was detected in 5 of 20 patients with acute or chronic remitting polyneuritis and in 4 of 20 patients with polyneuropathy and paraproteinemia but not in patients with other types of neuropathy, neurologic disease, or immunologic disease. In three patients with IgM paraproteinemia, the complement-fixing activity resided in the IgM fraction; in one patient with chronic inflammatory polyneuritis, antibody activity resided in the IgG fraction. In the inflammatory polyneuropathies, antibody titers did not always correlate with disease activity. Sera from patients with remitting polyneuropathies reacted with either human or rabbit peripheral nerve myelin, but sera from patients with paraproteinemia reacted only with human myelin.

On acquired hemophilia A. A survey of 11 cases.

Acquired hemophilia A due to antibodies of factor VIII procoagulant activity is rare. This paper reports 11 such patients followed up for long periods. The exemplify various forms of associated disorders. Four of them have died from hemorrhages, 4 have had complete remission and 3 are still alive with persistent inhibitors. The inhibitor activity was recovered in the immunoglobulin fraction in all the patients studied. Various forms of treatment were tried but remission related to therapy was seen in only one woman affected post partum. Spontaneous remissions are common and the aim of therapy must be to control acute severe hemorrhage.