Biomedical subjects

A M Gader

Publications and source records attributed to A M Gader.

At least 19 recordsLinked to original sources

PubMed1998

Moyamoya syndrome with unusual angiographic findings and protein C deficiency: review of the literature.

We describe the findings in a six-year-old female with typical clinical symptoms of Moyamoya phenomena, but with an unusual angiographic appearance. The vertebral artery showed segmented occlusion in the upper cervical region, with reconstitution via collateral circulation through muscular branches. The carotid circulation showed involvement of the external carotid artery (ECA) branches and marked narrowing of the internal carotid arteries (ICA) bilaterally, suggesting that this disease is systemic in nature.

Brain↗

PubMed1997

The role of platelets in the coagulopathy of heatstroke- a study of platelet aggregation in heatstroke patients during the Makkah pilgrimage (Haj) to Makkah.

Platelet aggregation was undertaken in platelet rich plasma in 34 heat-stroke patients during the Muslim pilgrimage (Haj) to Makkah; 18 were males and 16 were females; their ages ranged from 36 to 80 years (mean SD = 58 10). Platelet aggregability, on arrival at the Heatstroke Centres, was markedly inhibited in response to adrenaline, collagen, arachidonic acid and ristocetin but not to ADP. Responses to decreasing ADP doses (20.0, 2.0, 1.0 and 0.5 micromol/l) showed hyperaggregability in 12 patients, inhibited responses in 16 and normal responses in 6 patients. Aggregation responses were not significantly different when comparing patients with bleeding manifestations ( n = 10), with those without bleeding ( n = 24). Haemostatic parameters including plasma fibrinogen, ATIII and platelet count, were markedly reduced in the two patient groups who showed hyperaggrebable and depressed aggregation responses, but not in those with normal responses. These results lead us to conclude that: (1) platelet activation is a frequent feature of heatstroke; (2) in heatstroke altered aggregation responses, whether hyperaggregable or depressed, occur simultaneously with a consumption coagulopathy.

Journal Article↗

PubMed1996

Coagulation inhibitors and fibrinolytic parameters in patients on peritoneal dialysis and haemodialysis.

Coagulation inhibitors and fibrinolytic parameters were studied in twelve patients on continuous ambulatory peritoneal dialysis (CAPD) and ten patients on haemodialysis (HD). Patients on CAPD exhibited higher levels of ATIII and proteins C and S than those on HD. No significant differences were noted in tPA and PAI levels. Both groups of patients showed higher levels of tPA than controls. Besides, patients on HD had significantly lower levels of ATIII and protein C than controls. PAI levels in both patient groups were similar to those of the controls, but tPA levels were higher in patients than in controls. These results indicate that HD is associated with marked diminution in the circulating levels of coagulation inhibitors. This is in contrast to CAPD patients who showed elevated levels of these inhibitors, despite their significant loss in the dialysate. The finding of enhanced fibrinolysis in both patient groups may be a natural protective mechanism against the development of a thrombotic tendency.

Adolescent↗

PubMed1994

Haemostatic variables in patients with unstable angina.

To assess the contribution of thrombus formation in the pathogenesis of unstable angina, we employed the recently developed assays of small fragments which reflect the degree of activation of various components of the haemostatic system. Such haemostatic measurements were undertaken in patients with unstable angina (n = 47) from the time of their admission to the coronary care unit (CCU) at 8-h intervals in the first 24 h and then daily for a total of 5 days. The results obtained were compared with healthy control values. Patients exhibited lower ATIII, prolongation of the APTT and TT, but not PT or the reptilase time, which is a consequence of heparinization. There was significant elevation of fibrinogen, factor VIII:C, von Willebrand factor:antigen and von Willebrand factor:ristocetin cofactor throughout the study period. There was also evidence of thrombin generation as indicated by the elevated levels of fibrinopeptide A (FPA) and thrombin-antithrombin complexes. The platelet release proteins, beta-thromboglobulin (BTG) and platelet factor 4 (PF4), were markedly elevated in the first 2 days and dropped gradually thereafter. The fibrinolytic inhibitor, plasminogen activator inhibitor (PAI), levels were elevated throughout. Proteins C and S, plasminogen and alpha 2-antiplasmin remained unchanged. It was concluded that in patients with unstable angina, there is significant activation of the clotting system and inhibition of fibrinolysis which confirms the existence of a tendency towards thrombus formation in patients with unstable angina.

Adult↗

PubMed1993

Pregnancy outcome in women with antiphospholipid antibodies.

The association of antiphospholipid antibodies (APA) or lupus anticoagulant (LA) and recurrent fetal loss (RFL) is well established; however, the spectrum of pregnancy outcome in relation to various therapeutic approaches versus placebo is unknown. We studied 49 women with RFL, 14 with immune thrombocytopenia (ITP) 13 of whom without a history of RFL, and 32 controls (all in the first trimester of pregnancy) for the presence of APA. Tests for APA were positive in 15/49 women with RFL (30%), 6/14 ITP (43%) and 2/32 controls (6%). Treatment in the APA positive patients consisted of: no treatment for the 8 patients who had no history of RFL (Group A; all 34 previous pregnancies successful), aspirin alone (Group B, 5 patients; all 30 previous pregnancies unsuccessful), aspirin with prednisolone (Group C, 9 patients; 69/80 previous pregnancies unsuccessful), or aspirin, prednisolone and immunoglobulin G for resistant cases (Group D, 4 patients, previously in Group C). 10/11 (90.9%), 3/7 (43%), 7/13 (53.8%) and 4/7 (57.1%) pregnancies were successful in Group A, B, C and D, respectively. There was a total of 19/45 (42%) failures including 3 pregnancies in one patient who failed to respond to all forms of therapy. This open study with small subgroups of patients draws attention to a wide range of pregnancy outcome in women with APA and to the fact that APA may serve only as a marker for a wide range of pathological conditions with variable degrees of disease severity. More studies are, however, needed to explore the real mechanism of RFL in women with APA and RFL, especially those who are resistant to therapy.

Abortion, Habitual↗

PubMed1992

Severe congenital dysfibrinogenemia (fibrinogen-Riyadh): a family study.

Congenital severe dysfibrinogenemia was discovered in a small Saudi family. Their single child exhibited abnormal severe bleeding tendency since birth and his coagulation profile revealed evidence of severe dysfibrinogenemia. The parents who were first-degree cousins and completely asymptomatic showed evidence of dysfibrinogenemia but to lesser degree than in their son. The child presented with large cephalohematoma and evidence of intracranial hemorrhage and left hemiparesis. He was treated with cryoprecipitate and his hematoma resolved, but his neurological deficit remained.

Acute Disease↗

PubMed1991

Low dose danazol is effective in management of erythropoietin induced thrombosis.

Two patients (one male and one female) with end stage renal disease on chronic hemodialysis were treated with recombinant human erythropoietin (r-HuEPO). Both patients developed significant clotting in the vascular access and extracorporeal circuits. Coagulation studies indicated that both patients acquired high levels of tissue-type plasminogen activator inhibitor (PAI) with deficiency in tissue-type plasminogen activator (t-PA) and consequent impaired fibrinolysis. Their fibrinolytic activity was normalized with danazol therapy in doses as low as 2-4 mg/kg given orally once daily. We conclude that r-HuEPO-induced thrombosis is associated with impaired fibrinolysis due to acquired elevation of PAI which can be effectively prevented by small doses of danazol.

Adult↗

PubMed1991

Haemostatic measurements in childhood nephrotic syndrome.

Blood coagulation and platelet aggregation were assessed in children with nephrotic syndrome who were divided into the following groups: (1) relapse without treatment: (2) relapse on steroids; (3) early remission; (4) late remission and (5) steroid resistant. The renal histological findings were also recorded. Plasma anti-thrombin III (ATIII) levels were markedly reduced in groups 1 and 2, below normal in group 3 and were normal in groups 4 and 5. There was significant urinary loss of ATIII in groups 1 and 2 as well as in group 5. Plasma fibrinogen fluctuations exhibited the expected negative correlations with plasma ATIII. Reptilase time showed significant prolongation in groups 1, 2 and 3, and was near normal in groups 4 and 5. Platelet aggregation in response to arachidonic acid exhibited aggregation followed by disaggregation in groups 1, 2, 4 and 5, and was normal in group 3. Hyperaggregation in response to decreasing doses of ADP was noted in all patient groups as well as controls with no relationship to serum albumin levels. Aggregation responses to collagen and ristocetin were normal. It is concluded that: 1. The fluctuations in ATIII levels in childhood nephrotic syndrome are determined by the response to steroids and not by the renal histology per se. 2. An acquired fibrin polymerization defect (dysfibrinogenaemia) and an abnormality of the prostaglandin pathway of platelet activation, both reversible, are yet other haemostatic abnormalities in childhood nephrosis. 3. The discrepancies in the literature on haemostatic parameters, specially ATIII in childhood nephrosis, would not have arisen if their fluctuation in relation to steroid therapy as well as the renal histological features of nephrotic syndrome had been documented simultaneously.

Adolescent↗

PubMed1991

Significant elevation of protein C and protein S levels in thrombotic disorders by low dose danazol.

Six patients (three males and three females), mean age 35.2 years (range 31-43 years), with extensive venous thrombosis were studied. Initial laboratory data indicated that all patients had normal antithrombin III (ATIII), four patients had low protein C (PC), three patients had low protein S (PS) and two patients had low plasminogen. Four patients had high fibrinogen and all patients had reduced tissue-type plasminogen activator activity, elevated tissue plasminogen activator inhibitor and low fibrinolytic activity. All patients were treated with danazol, 5-7 mg/kg orally once daily. In all patients there was significant elevation of ATIII, PC, PS, and plasminogen, reduction in plasma fibrinogen and PAI and enhancement of fibrinolysis. During the 12-36 months period of follow-up, there were no symptoms or signs that suggested recurrence of thrombosis. Apart from weight gain of 5-10 kg and disturbed menstrual cycle in two women, no major side effects were seen. These data suggest that danazol is potentially useful therapy that may increase levels of natural anticoagulants in patients with thrombotic illnesses in which ATIII, PC and PS are low or normal. Further studies are needed to confirm these observations.

Adult↗

PubMed1991

Effect of recombinant human erythropoietin (rHuEpo) on the hemostatic system in chronic hemodialysis patients.

Hemostatic measurements were undertaken in eight chronic hemodialysis uremic patients on recombinant human erythropoietin (rHuEpo). Same measurements were repeated in another seven patients in whom anemia was corrected by the transfusion of red blood cells. The correction of the anemia by rHuEpo therapy was accompanied by 1. correction of the prolonged Simplate Bleeding Time (BT) to normal less than 10.0, minutes after 16 weeks of rHuEpo treatment; 2. significant increases in the levels of fibrinogen, clotting FVIII:C, vWF:antigen, vWF:ristocetin cofactor and platelet count; 3. enhanced aggregation responses to ADP, adrenaline, arachidonic acid, collagen and ristocetin. There was no significant fluctuation in other coagulation parameters PT, APTT, TT, reptilase time and antithrombin III and plasma fibrinogen. In patients who were treated with RBC transfusion and despite the correction of the anemia, the bleeding time shortened significantly but not corrected, mean BT before and after RBC transfusion was 17.1 +/- 1.4 and 11.6 +/- 1.9 minutes respectively. Besides there was significant elevation of vWF:Ricofactor levels but not FVIII:C, vWF:Ag or platelet count. Platelet aggregation responses to ADP remained unchanged. It is concluded that significant elevations of FVIII:related activities, plasma fibrinogen, improved platelet aggregability and correction of the BT are salient hemostatic changes that follow rHuEpo therapy in uremic patients.

Adult↗

PubMed1990

Direct activation of platelets by heat is the possible trigger of the coagulopathy of heat stroke.

The trigger of the coagulopathy that complicates heat stroke is obscure, but direct platelet activation by heat is a possibility we set out to study. Platelet rich plasma (PRP), prepared from blood donors, was incubated at increasing temperatures (38-45 degrees C) and then platelet aggregation was undertaken in response to decreasing low doses of ADP (less than 2.0 mumol/l). Hyperaggregability was manifested when the incubation temperature reached 43 degrees C and was maximum at 44 degrees C before complete inhibition of responses at 45 degrees C. The platelet hyperactivity induced by heating at 44 degrees C persisted after reincubating PRP samples at 37 degrees C. These platelet responses could not be triggered in PRP samples prepared from subjects after the overnight ingestion of aspirin or after the addition of aspirin to PRP before starting the heating procedure. However, aspirin was less effective when added to PRP after the appearance of the heat-induced hyperaggregability. In conclusion, these results indicate that platelets can be activated directly by heat. This mechanism which may be operational in heat stroke, is unaffected by cooling (body cooling being basic in the management of heat stroke) but can be prevented by the early administration of aspirin.

Adenosine Diphosphate↗

PubMed1990

Interaction between nabumetone--a new non-steroidal anti-inflammatory drug--and the haemostatic system ex vivo.

Twenty-six healthy volunteers were given the non-steroidal anti-inflammatory drug nabumetone (1 g/day p.o.) for 10 days. Platelet aggregation tests in response to adenosine diphosphate, adrenaline, collagen, arachidonic acid, and ristocetin and bleeding time and coagulation screening tests were performed on three occasions: (1) before drug therapy; (2) on the last day of drug therapy, and (3) 5 days after the end of therapy. No significant changes were noted in platelet aggregation, bleeding time, or the coagulation screening tests, except for a significant drop in fibrinogen during therapy and for 1 week after stopping the drug. The lack of any antiplatelet action and minimal effects on the coagulation parameters recommend the drug as a suitable antirheumatic in patients with bleeding disorders. The hypofibrinogenaemic action requires further studies.

Adult↗

PubMed1989

Blood coagulation changes in liver disease.

The study describes the results of prothrombin time (PT), Anti-thrombin III (AT III) and fibrin polymerization curve (FPC) measured simultaneously in patients with liver disease who were divided into two groups: cirrhotics (n = 37) and miscellaneous liver disease (n = 35). There was significant prolongation of PT in 82% of cirrhotics and in 17% of the miscellaneous liver disease group. In contrast significant reduction of AT III levels was noted in 94% of cirrhotics and 31% of the miscellaneous liver disease group. Abnormal FPC was seen in 88% and 32% respectively. There was a good correlation between PT and AT III levels. It was concluded that AT III measurement is a more sensitive indicator than PT and FPC in the assessment of hepatocellular dysfunction.

Adult↗

PubMed1988

Dose-response aggregometry in maternal/neonatal platelets.

The aggregation of platelets collected from maternal/neonatal pairs (n = 240) at the time of childbirth, was studied in response to multiple doses of ADP, collagen, arachidonic acid and ristocetin. Similar responses were obtained from healthy nonpregnant adult controls for comparison. The lag phase, slope of the aggregation curves as well as maximum aggregation (MA%) were recorded and analysed. Neonatal and adult platelets exhibited more enhanced responses to decreasing doses of ADP, arachidonic acid and ristocetin, than maternal platelets. These enhanced responses were exhibited more consistently in the slopes of the aggregation curves than in MA%. Although neonatal platelets have shown longer lag phase in their responses to collagen, the rate of the aggregation reaction was significantly faster than maternal platelets, with no differences in MA%. These results contradict many previous reports suggesting impaired aggregation responses of neonatal platelets to these agonist. The possible reasons for these contradictions were discussed.

Adenosine Diphosphate↗

PubMed1987

Coagulation changes in sickle cell disease in early childhood.

Measurements of the coagulation system were carried out in children with sickle cell disease (SCD) in both steady state and on the 1st day of painful crisis and were compared to age- and sex-matched healthy controls. No significant differences were found in prothrombin time, partial thromboplastin time, thrombin time, reptilase time, plasma fibrinogen, antithrombin III, factor VIII:C, ristocetin-cofactor (Ri-Cof) and platelet aggregation responses to ADP, collagen and adrenaline. Abnormal aggregation responses to ristocetin were noted in all patients with SCD when compared to controls. Daily measurements during the first 4 days of painful crisis showed significant elevation of fibrinogen and Ri-Cof and enhancement of aggregation to ADP and adrenaline by the 3rd day of crisis. It was concluded that the changes noted, rather than being primarily responsible for the onset of crisis, can only be secondary changes arising from the aetiological factors of crisis, i.e. stasis and acute-phase proteins.

Anemia, Sickle Cell↗

PubMed1985

Combined factor V and factor VIII deficiency with normal protein C and protein C inhibitor. A family study.

Combined deficiency of factor V and factor VIII, a rare bleeding disorder, is reported in a Syrian family. 2 siblings, 10 and 6 yr old are affected. They had mild bleeding manifestations. Their prothrombin time and partial thromboplastin time were prolonged, but thrombin time was normal. Both had low levels of factor V, (6% and 7%), factor VIII, (both 10%) factor VCAg (both 6%) and factor VIII CAg, (6% and 4%). All members of this family had normal levels of factor VIIIR:Ag, protein C, antigen and protein C inhibitor. The normal levels of protein C and protein C inhibitor in the 2 affected family members indicate that the combined deficiency of factors V and VIII has nothing to do with protein C. This contrasts with previous reports that deficiency of protein C inhibitor is the cause of combined factor V and factor VIII deficiency. The probable mode of inheritance of this defect is discussed.

Blood Coagulation Factors↗

PubMed1985

Antithrombin III (AT III) and fibrinogen levels in nephrotic syndrome in children.

Plasma antithrombin III (AT III) and fibrinogen were measured in 25 Saudi children with nephrotic syndrome during both relapse and remission. During relapse the mean AT III level was 46.6% (range 7-84%) and mean fibrinogen was 992 mg/dl (range 413-1,433), while during remission, AT III levels increased remarkably to a mean value of 120.6% (range 81-160) and plasma fibrinogen dropped to a mean level of 431 mg/dl (range 230-693). In 10 of these patients AT III was measured simultaneously in urine. During relapse urine AT III levels were of the same magnitude as plasma AT III, while during remission no AT III was detected in urine. These findings confirm the hypercoagulable state during the relapse of nephrotic syndrome and the quick recovery during remission. None of our patients showed any clinical evidence of thromboembolism. Loss of AT III in urine during relapse and/or its consumption is the probable cause of low AT III during relapse while excessive production of AT III by liver probably accounts for the high levels in remission.

Antithrombin III↗

PubMed1982

The potentiating effect of cortisone (prednisolone) on the fibrinolytic and clotting factor VIII responses to intravenous infusion of adrenaline in man.

In an attempt to investigate the effect of the proposed interaction between corticosteroids and adrenaline in stressful situations on fibrinolysis and coagulation, blood plasminogen activator and clotting factor VIII were measured before and after a prolonged adrenaline infusion (3.5 micrograms/min for 30 min) in 4 asthmatic patients on long-term corticosteroid (prednisolone) therapy and their responses were compared with healthy controls. Asthmatic patients showed greater responses of both parameters to adrenaline than controls indicating that long-term corticosteroid treatment enhances the acute responses of plasminogen activator and clotting factor VIII to adrenaline infusion.

Asthma↗