Low adjusted-dose acenocoumarol therapy in sickle cell disease: a pilot study.

Vasoocclusion is a continuous process in sickle cell disease (SCD) and accumulates to significant end organ damage, mostly irrespective of the occurrence of manifest acute vasoocclusive events. As there are indications that reversing the hypercoagulable state may be of clinical benefit in sickle cell patients, we performed a randomized, double blind, placebo-controlled, cross-over pilot study to assess the efficacy and safety of low-adjusted dose acenocoumarol therapy (International Normalized Ratio: 1.6-2.0) in SCD. Treatment consisted of either acenocoumarol or placebo for 14 weeks, after which treatment was discontinued for a period of five weeks. Then, patients initially on acenocoumarol received placebo (and vice versa) for 14 weeks. Therapy efficacy was assessed by comparing the frequency of vasoocclusive complications, the occurrence of bleeding, and clotting activation between acenocoumarol and placebo treatment of each individual patient. Twenty-two patients (14 homozygous [HbSS] and 8 double heterozygous sickle-C [HbSC]; aged 20-59 years) completed the entire study. Acenocoumarol treatment did not result in a significant reduction of acute vasoocclusive events (three painful crises during acenocoumarol, five painful crises during placebo). There was a marked reduction of the hypercoagulable state (depicted by a decrease in plasma levels of prothrombin F1.2 fragments [P = 0.002], thrombin-antithrombin complexes [P = 0.003], and D-dimer fragments [P = 0.001]) without the occurrence of major bleeding. Even though no clinical benefit (pertaining to the frequency of painful crises) was detected in this pilot study, the value of low adjusted-dose acenocoumarol for preventing specific events (such as strokes) and as a long-term treatment of sickle cell patients should be subject of further study.

[Sickle cell anemia during pregnancy]. / Sikkelcelanemie tijdens de zwangerschap.

A 31-year-old pregnant Creole woman with sickle-cell anaemia went through a crisis of acute cholecystitis at 29 weeks' amenorrhoea. The crisis subsided after cholecystectomy, at which relative reduction of the number of sickle-cells by blood transfusions, adequate oxygenation, fluid, and antibiotic prophylaxis were provided. After 35 weeks' amenorrhoea, a healthy son was delivered by caesarean section. After the delivery, she developed fever and abdominal aches with a wound infection, and 10 days later a generalized epileptic attack. She recovered without sequelae. Pregnancy in a woman with sickle-cell anaemia may induce a sickle-cell crisis. The maternal morbidity and mortality and perinatal mortality are high, in spite of a pronounced decrease due to improved care.

[Poisoning with toxic plants in Curacao in 1766]. / Vergiftiging met toxische planten op Curaçao in 1766.

In the spring of 1766 a black supervisor in Curaçao was the victim of attempted poisoning by a black practitioner or curador, engaged by two persons caught stealing by the supervisor. Data on the case were preserved in a letter from the Curaçao director to the managers of the West-Indian Company in Amsterdam. In retrospect, the symptoms of the intoxication indicate that a similar mixture of toxic plants was used as described in 890 A.D. by the Arabic medical writer Wahshiya in his 'Book of Poisons': Calotropis procera and Pithecellobium unguis cati.

Low-intensity oral anticoagulation in sickle-cell disease reverses the prethrombotic state: promises for treatment?

Increased plasma levels of prothrombin fragment 1 + 2 (F1 + 2) found in patients with sickle-cell disease reflect enhanced endogenous thrombin generation. We postulate that hypercoagulability contributes to vaso-occlusion. The intensity of acenocoumarol treatment required to reduce the F1 + 2 level to 50% of pretreatment level was investigated in seven patients with symptomatic sickle-cell anaemia during steady-state disease for a period of 2 months. All patients had increased levels of F1 + 2 compared with an age-matched control group. Normalization of the F1 + 2 was achieved at a median INR of 1.64 (range 1.18-2.2). It is concluded that low-intensity oral anticoagulation normalizes the hypercoagulability in sickle-cell disease.

Prophylaxis of delayed nausea and vomiting after cancer chemotherapy.

OBJECTIVE: To compare ondansetron and domperidone for treatment of delayed nausea/vomiting (DN/V) following highly emetogenic chemotherapy, after attaining total suppression of emesis on the day of chemotherapy by mean of ondansetron (combined with dexamethasone in the case of cisplatin-treated patients). METHODS: Domperidone (3 x 20 mg daily) was compared with ondansetron (3 x 8 mg daily) in a randomized double-bind placebo-controlled study. Out of 65 consecutive patients who received a first course of either cyclophosphamide and cisplatin for advanced stage ovarian cancer or cyclophosphamide, doxorubicin and 5-fluoro-uracil for metastatic breast carcinoma, 60 patients were eligible for entering the study. According to data from the literature these chemotherapeutic regimens with induce DN/V to a comparable degree. The patients were questioned daily from day 2 through day 5 by the same investigator and the severity of nausea or vomiting was scored on a numerical scale. RESULTS: Emesis was totally suppressed in all patients on the day of chemotherapy. As to DN/V, 16 out of 20 patients receiving placebo required "rescue" medication versus none in the other two groups (p < 0.001). Only 2 (10%) patients were symptomatic with domperidone versus 9 (45%) symptomatic patients in the ondansetron-treated group (p < 0.05). CONCLUSIONS: Both drugs are effective, but domperidone (3 x 20 mg) is more effective than ondansetron (3 x 8 mg) for the prevention of the delayed nausea and/or vomiting which occur after highly emetogenic chemotherapy (p < 0.05).

Maternal death due to acute necrotizing colitis in homozygous sickle cell disease.

The case history is described of a 21-year-old female with homozygous sickle cell disease and fatal postpartum haemorrhage from the colon. At autopsy many sickled cells were found in the arterioles of the mucosa and submucosa in combination with necrotic lesions and ulcerations of the sigmoid colon. A causal association between occlusion of blood vessels by sickled cells and the occurrence of vascular necrosis of the sigmoid colon is suspected.

[Acute psychosis in a patient with a combination of sickle cell disease and hemoglobin-C disease]. / Acute psychose bij een patiënt met een combinatie van sikkelcelziekte en hemoglobine C-ziekte.

A 35-year-old negroid patient, known to have sickle cell-haemoglobin C disease, after heavy exercise developed an acute thrombotic crisis localised mainly in the brain. The clinical manifestations were those of an acute psychosis with severe confusion, aggressiveness, unco-operative behaviour and incontinence for faeces and urine. With adequate therapy he recovered after a few days. This so-called cerebral sickle cell crisis, confirmed by multiple small encephalomalacia lesions on the MRI which are typical of this disease, is a rare complication and difficult to diagnose.

[Severe deglutition disorders and iron deficiency; Plummer-Vinson syndrome]. / Ernstige slikstoornissen en ijzerdeficiëntie; het syndroom van Plummer-Vinson.

At oesophagogastroscopy a web was seen in the upper oesophagus in a female of 73 years with dysphagia. Because she also had a smooth tongue, a low serum iron level and anaemia, the syndrome of Plummer-Vinson was diagnosed. After treatment with ferrous fumarate the dysphagia, the web and the anaemia disappeared and the serum iron rose. The symptomatology of this syndrome is discussed. Remarkably, the pathogenesis is not completely known. There are indications that this uncommon syndrome is a premalignant disorder.

Imaging the bone marrow with magnetic resonance during a crisis and in chronic forms of sickle cell disease.

Five patients with sickle cell disease have been studied by magnetic resonance imaging (MRI) in three instances during a crisis. Attention was directed to the pelvis and lower extremities. Bone marrow pathology has been classified according to generalised or circumscribed alterations in signal intensity on T1 weighted spin-echo sequences. Both acute and chronic changes were observed.

[Kidney tubule dysfunction caused by acetic acid]. / Niertubulusfunctiestoornissen door azijnzuur.

Two patients admitted after ingestion of 80% acetic acid are described. Only the first patient developed haemolysis, slight intravascular coagulation and oliguric kidney insufficiency. They were treated with a nasogastric tube and total parenteral feeding. During the first week after admission urinary excretion of beta 2-microglobulin, alanine-aminopeptidase and N-acetyl-glucosaminidase was significantly increased. The patients remained haemodynamically stable and did not develop fever. The above-mentioned elevated excretions returned to normal levels. Both patients showed similar patterns of tubular proteinuria. The observations in the second patient suggest a direct toxic effect of acetic acid on the proximal tubule of the kidney.