Thrombotic thrombocytopenic purpura in southern Turkey: a single-center experience of 29 cases.

In this retrospective, nonrandomized study, we describe our experience in the management of 29 consecutive patients with thrombotic thrombocytopenic purpura (TTP) treated with a combined therapy of plasma exchange (PE) and steroids at a single center. We compared the effectiveness of high-dose steroids (20-25 mg/kg methyl prednisolone) as first-line treatment in combination with PE therapy with the combination of standard-dose steroids (1 mg/kg methyl prednisolone) and PE in adult patients with TTP. Clinical, laboratory data and treatment outcomes such as response rate, median time to recovery and survival were evaluated retrospectively. Overall (OR) and complete (CR) response rates were 69 and 52% respectively. Similar response rates were found in patients treated with pulse or conventional dose steroids; however, the median time to response was delayed in the high-dose methyl prednisolone (HDP) group. The median time from the initiation of symptoms to initiation of treatment was approximately 15 days (range: 0-30). Delayed treatment in our patients because of delayed referral to our center resulted in poor response to treatment. In all, four of 14 (27%) complete responders experienced relapses. The predicted relapse rate was 48% at a median of 30 months. All the relapses presented with a combination of thrombocytopenia and microangiopathic hemolytic anemia. This analysis showed that high-dose steroid treatment did not prove to be beneficial for TTP patients as firstline therapy combined with PE. Moreover, pulse steroid interventions might have resulted in delayed responses and our data suggest that initiation of treatment with PE should not be delayed.

Levels of malondialdehyde, glutathione and ascorbic acid in idiopathic thrombocytopaenic purpura.

BACKGROUND: Idiopathic thrombocytopaenic purpura (ITP) is an autoimmune disorder, which causes an acute or chronic thrombocytopenia, and may result in potentially life-threatening haemorrhage. Oxidative damage may be involved in the pathogenesis of autoimmune diseases. Antibodies to bind to membrane lipids and platelet destruction may play a role on lipid peroxidation in ITP. OBJECTIVES: To investigate the posible role of lipid peroxidation and antioxidants in patients with ITP. DESIGN: The levels of plasma and erythrocyte malondialdehyde (MDA), erythrocyte glutathione and ascorbic acid were analysed in patients with ITP. METHODS. The MDA levels were performed according to the method of Bidlack WR. Plasma MDA, erythrocyte glutathione and ascorbic acid levels were carried out according to the methods of Ohkawa H, Beutler E and Bauer JD, respectively. RESULTS: The erythrocyte and plasma MDA levels in patients with ITP were found to be 9.52+/-4.65, 3.03+/-1.44 (p<0.001) and in control group were found to be 2.49+/-0.57, 1.03+/-0.28 nmol/ml (p<0.001), respectively. Erythrocyte glutathione was found to be 3.71+/-0.82, 6.26+/-0.66 micromol/gr Hb (p<0.001). Ascorbic acid levels of these groups were 1.09+/-0.25, 1.70+/-0.33 mg/dl (p<0.001). CONCLUSION: The oxidative damage is involved in the pathogenesis of ITP. In patients with ITP, the platelet destruction and bleeding may play significant role on elevation of lipid peroxidation and reduction of antioxidant capacity. Further studies on oxidant and antioxidant status of ITP are also needed to confirm these results.

Value of duplex and color doppler ultrasonography in the evaluation of orbital vascular flow and resistance in sickle cell disease.

The aim of the present study was to assess and to compare the orbital and retinal vascular flow dynamics and resistance in patients with homozygous sickle cell disease with controls by means of duplex and color Doppler ultrasonography. Forty-six patients with homozygous sickle cell disease (SCD) and 20 healthy subjects were included in the study. None of the patients had objective signs of ocular involvement. Duplex and color Doppler ultrasonography of the ophthalmic, short posterior ciliary, and central retinal arterial flows of the both eyes were performed to assess peak systolic flow velocity (PSFV), end-diastolic flow velocity (EDFV), and mean flow velocity (MFV) through entire cardiac cycle with further calculation of resistive indices (RI) and pulsatility indices (PI). Ophthalmic arterial flow velocities were significantly increased in patients with SCD than in controls (P < 0.0001). Blood flow velocities of the central retinal artery were found to be significantly reduced (P < 0.0001) while RI and PI values were markedly higher (P < 0.02 and P < 0.03) in patients with SCD compared to controls. Reduction of retinal vascular flow velocities and increase of retinal vascular resistance were significantly related to the mean hemoglobin and hematocrit levels, red blood cell count, and mean corpuscular hemoglobin volume (P < 0.009, P < 0.01, P < 0.02, and P < 0.04, respectively). In conclusion, Doppler ultrasonography in patients with SCD who had no objective signs of ocular involvement allowed detection enhancement of ophthalmic flow velocities, reduced retinal flow velocities, and increased retinal vascular resistance, which are associated with haematological features.

The Levels of Sera Malondialdehyde, Erythrocyte Membrane Na+-K+/Mg++ and Ca++/Mg++ Adenosine 5' Triphosphatase in Patients with Sickle Cell Anemia.

The various membrane abnormalities of sickle erythrocytes may result from excessive accumulation of oxidant damage. We measured the sera levels of malondialdehyde, products of lipid peroxidation, Na+-K+/Mg++ Adenosine 5' triphosphatase (ATPase) and Ca++/Mg++ Adenosine 5' triphosphatase, erythrocyte membrane enzymes, in patients with sickle cell anemia and compared their levels with that of normal controls. MDA, Na+-K+/Mg++ and Ca++/Mg++ ATPase levels of control groups were 0.90 ± 0.04 nmol/mL, 168 ± 12.9 and 140.6 ± 8.2 nmol Pi/mg prot/hour, respectively. MDA, Na+-K+/Mg++ and Ca++/Mg++ATPase levels of patients were 2.02 ± 0.01 nmol/mL, 127.0 ± 8.4 and 110.0 ± 9.6 nmol Pi/mg prot/hour, respectively. Our experimental results showed that there was a significant increase in MDA levels of patients with sickle cell anemia as compared with that of the controls. However, erythrocyte membrane Na+-K+/Mg++ and Ca++/Mg++ ATPase levels of patients with sickle cell anemia were significantly lower than the, Na+-K+/Mg++ and Ca++/Mg++ ATPase levels of normal controls.

Bone marrow necrosis in antiphospholipid syndrome.

Bone marrow necrosis (BMN) is a relatively rare entity and has been associated with a poor prognosis. It is most commonly found in patients with neoplastic disorders, severe infections and sickle cell anemia. An unusual case of antiphospholipid syndrome (APS) with extensive bone marrow necrosis is described in a 27 year old woman. The patient presented with severe pancytopenia, some cognitive impairment resulting from a previous cerebrovascular accident, fever, hypertension, dyspnoea, tachycardia, hepatosplenomegaly, and vaginal bleeding. Her laboratory findings included a strongly positive Coombs' test (anti-IgG and anti-C3d), a prothrombin time of 23 seconds and an activated partial thromboplastin time of 45 seconds. Anticardiolipin antibody tests were positive. Antinuclear and anti-DNA antibodies were negative but the anti-SM test was positive. A bone marrow biopsy specimen was reported as showing extensive necrosis. The patient was treated with steroids, transfusion, and plasma exchange with some clinical improvement but her pancytopenia did not respond and necessitated frequent transfusions. This case lends further support to the association between APS and BMN.

Spectral pulsed Doppler sonography of renal vascular resistance in sickle cell disease: clinical implications.

The major complications in sickle cell disease (SCD) are microcirculation lesions and impairment of renal function. The aim of this study was the evaluation of renal vascular resistance by means of spectral pulsed Doppler sonography and its relationships with haematological and clinical features in patients with SCD. 40 patients with SCD (mean age 22.4 +/- 7.0) and 14 age and sex matched healthy subjects (mean age 25.7 +/- 9.5) were included into the study. Spectral Doppler sonography of main renal, segmental and interlobar arteries were performed on both kidneys in all patients and controls. Peak systolic, end diastolic and mean velocities through the entire cardiac cycle were obtained, with calculation of the resistive (RI) and pulsatility (PI) indices. All the patients were investigated in stable state conditions and had not been transfused within a month before investigation. Patients were followed for up to 6 months. Patients with SCD had higher values of RIs and PIs than control subjects (p < 0.0001, p < 0.0001, respectively). Patients with high value of RIs (RI > 0.70) had more pronounced disturbances of blood parameters (all p < 0.05), than patients with normal RIs (RI < 0.70). Significant positive correlation existed between RIs and ISC number, MCHC level (r = 0.52, p < 0.001 and r = 0.42, p < 0.01), while RBC count and Hb level correlated inversely with RIs (r = -0.39, p < 0.01 and r = -0.42, p < 0.01). During follow-up, nine patients (33.3%) with high RIs and only one patient (5.5%) with normal RI developed painful crises. In conclusion, renal vascular resistance, assessed by Doppler sonography was raised in SCD patients as compared with age matched apparently healthy persons. These changes were more pronounced in those with more severe manifestations of disease and correlated with haematological and clinical features of sickle cell disease.

Bencyclane as an anti-sickling agent.

A vasodilating Ca2+ channel blocker, bencyclane, was used in 18 patients with homozygous sickle cell anaemia (SCD) to test the possible anti-sickling effect. With bencyclane intervention the Na(+)-K+ ATPase activity increased from 256 +/- 29 to 331 +/- 37 nmol Pi/mg protein/h (P < 0.0001) and the Ca(2+)-Mg2+ ATPase level increased from 172 +/- 12 to 222 +/- 44 nmol Pi/mg protein/h (P < 0.0001). The intracytoplasmic Ca2+ concentration reduced from 3.5 +/- 0.6 to 2.7 +/- 0.25 mumol/l (P < 0.0001). The patient's blood contained fewer irreversibly sickled cells (ISCs) (a reduction from 21.4% to 14.4%) (P < 0.05). At the same time MCHC of the erythrocytes decreased from 34.5 to 33.0 g/dl (P < 0.05). Bencyclane appears to be a promising anti-sickling agent that can be used orally in SCD.

The frequency of anaemia, iron deficiency, hemoglobin S and beta thalassemia in the south of Turkey.

A survey on the prevalence of anemia, iron deficiency, and hemoglobinopathies (Hb S and beta thalassemia) was carried out in an ethnically mixed and carefully registered population of 45,000 living in an area in the Southern Turkey. A total of 1223 subjects (representing the population with respect to sex and age group) were surveyed. The rate of anemia was found to be 16.9% overall with a highest prevalence of 18.3% in the children (0-2 ages) and 16.3% in the 14+ age group. The prevalence of iron deficiency using low transferrin saturation as criteria was found to be 17.2% overall, being 48.0% in the infant group, 19.6% in the children, and 14.7% in the 14+ age group. The rate of Hb S using the sickling test was found to be 3.9% in the entire population without separating for ethnic groups. It was more prevalent (9.6%) in the Arabic speaking and not found at all in the Kurdish speaking people. The rate of beta thalassemia with a high HbA2 was 3.4% overall and highest (7.1%) in the Kurdish speaking people.