Peter Tsang

Treatment of Antiphospholipid Antibody Syndrome (APS) in Pregnancy: A Randomized Pilot Trial Comparing Low Molecular Weight Heparin to Unfractionated Heparin

OBJECTIVE To compare low molecular weight heparin (LMWH), specifically dalteparin, to unfractionated heparin (UFH) for the treatment of antiphospholipid antibody syndrome (APS) in pregnancy. METHODS In a tertiary referral centre, 28 women met the 1999 International Consensus Criteria for APS, based on their obstetrical history and APS serology. The women were randomized, using a random numbers table with blocks of 12, to receive either prophylactic dosing of dalteparin or UFH starting either preconceptionally or early in pregnancy. All women also received low-dose acetylsalicylic acid, started preconceptionally. The primary outcome was a live birth. The secondary outcomes were maternal and fetal complications. RESULTS Of the 14 women who received the LMWH, dalteparin, and the 14 women who received UFH, 1 woman in each group did not conceive. Nine of the 13 women (69%) given dalteparin had a successful pregnancy (95% confidence interval [CI], 39-91%), compared to 4 out of the 13 women (31%) in the UFH group (95% CI, 9-61%). Nine women in total had spinal or epidural anaesthesia, and there were no complications overall. CONCLUSION Dalteparin may be an effective alternative to UFH for treatment of APS in pregnancy. A multicentre randomized trial is needed to determine benefit-to-risk ratios for the use of dalteparin and UFH to treat this high-risk obstetrical condition. Pharmacokinetic and pharmacodynamic studies are also recommended to maximize therapeutic response and minimize toxicity.

Fusion of PRKG2 and SPTBN1 to the platelet-derived growth factor receptor beta gene (PDGFRB) in imatinib-responsive atypical myeloproliferative disorders.

Chromosomal translocations involving the platelet-derived growth factor receptor beta gene (PDGFRB) have been reported in a subset of patients with atypical myeloproliferative disorders (MPDs). The fusion of the PDGFRB gene, which encodes a tyrosine kinase receptor, with different partner genes results in its constitutive activation. We present the cases of two patients with atypical MPD carrying t(4;5)(q21;q33) and t(2;5)(p21;q33), respectively. Fluorescence in situ hybridization demonstrated that PDGFRB was involved in both translocations. Further characterization of the 4q21 breakpoint using a bacterial artificial chromosome probe revealed PRKG2 as the likely gene partner to PDGFRB. Characterization of the 2p21 breakpoint identified a novel gene partner to PDGFRB, the SPTBN1 gene. Both patients achieved a complete molecular remission after introduction of imatinib mesylate therapy.

Catastrophic antiphospholipid syndrome presenting with pulmonary hemorrhage: case report

This is a case report of catastrophic antiphospholipid syndrome (APLS) involving the rare manifestation of pulmonary hemorrhage. This rare variant of APLS is frequently life threatening despite medical therapy. The pathogenesis of pulmonary hemorrhage in catastrophic APLS remains incompletely understood. The optimal approach to managing pulmonary hemorrhage in the setting of catastrophic APLS is still unclear, however this case report demonstrates the success of combination therapy with anticoagulation, corticosteroids and plasma exchange.

Extreme eosinophilia in a setting of metastatic leiomyosarcoma: an unusual case report.

Dear Editor, We describe a case of extreme eosinophilia caused by an underlying metastatic uterine cancer. A 56-year-old female presented with dyspnea, dry cough, right-sided chest pain, skin rashes, fatigue, decreased appetite, and weight. Past history was significant for uterine fibroids, noted to increase in size months prior to presentation. She was tachycardic and had large suprapubic mass but vaginal exam was noncontributory. Liver and spleen were not palpable. Investigations, revealed leukocytosis at 83.7×10/L, neutrophilia at 36.74× 10/L, eosinophilia at 40.67×10/L, and monocytosis at 3.10×10/L. Occasional hypogranular eosinophils were seen on blood smear but no circulating blasts. Electrocardiogram showed sinus tachycardia with non-specific T wave changes. Echocardiogram was normal. Stool was positive for blastocystis hominis. Bone marrow revealed granulocytic and eosinophilic hyperplasia with no increased blasts or atypical lymphocytes. Underlying mast cell disease was ruled out using immunophenotyping and tryptase stain. Cytogenetic analysis showed normal female karyotype and cKIT mutation and FISH studies for t[9;22], FIPLIL1-PDGFRA and PDGFRB were negative. Interestingly, imaging studies revealed right upper lobe mass, multiple pulmonary nodules, and a large uterine mass causing bilateral hydronephrosis. Bronchial biopsy showed poorly differentiated nonsmall cell carcinoma, nonpulmonary in origin, with a background of extensive necrosis and tissue eosinophilia. Core biopsy of the pelvic mass showed extensive necrosis and CA-125 was at 240 kU/L [<35] Although the diagnosis of leiomyosarcoma could not be confirmed, it could not be excluded. She was started on hydroxyurea 500 mg BID and prednisolone 50 mg OD and was planned to have resection of the pelvic mass, but suffered rapid decline in her respiratory status. Palliative radiation to the lung mass was initiated. Her eosinophilia, however, continued to worsen, reaching a WBC of 213×10/L with eosinophils of 174×10/L 2 months after presentation. Hydroxyurea was increased to 1,500 mg and low dose imatinib at 100 mg daily was initiated with no effect. She progressively declined with recurrent dyspnea, development of left brachiocephalic, and internal jugular veins thrombosis and eventually passed away. Autopsy confirmedmetastatic uterine leiomyosarcoma locally invasive and widely metastatic to the lungs, liver, spleen, diaphragm, thoracic, and pelvic lymph nodes. She had evidence of eosinophilia-induced acute lung injury and hypercoagulable state manifested by myocardial ischemia with widely patent coronary arteries. Rare microscopic thrombi were seen in the vasculature of the lateral left ventricle and arterial appendages. She was also found to have left brachiocephalic deep venous thrombosis and several brain microvascular intraluminal thrombi with prominent eosinophils within the clot (Fig. 1). A. Z. Al-Riyami Division of Hematological Pathology, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada

Hyperferritinemia in the Chinese and Asian community: A retrospective review of the University of British Columbia experience

BACKGROUND AND METHODS Elevated serum ferritin is a common clinical finding. The etiology of hyperferritinemia in the Asia-Pacific population is less clear due to a low prevalence of known HFE mutations such as C282Y and H63D, as well as an increased prevalence of viral hepatitis and hereditary anemia. A retrospective case review of 80 patients of Asian ethnicity referred to three subspecialists in tertiary care teaching hospitals between January 1997 and March 2005 for assessment of hyperferritinemia was performed. RESULTS Only four patients (5%) had iron overload on liver biopsy or quantitative phlebotomy. Forty-nine patients (61%) had secondary causes for their hyperferritinemia, of which 26 had liver disease; 16 of those patients also had viral hepatitis. Thirteen patients fulfilled criteria for the insulin resistance syndrome. Other causes included hematological disorders (n=10), malignancy (n=2) and inflammatory arthritis (n=2). Twenty-seven cases (34%) of unexplained hyperferritinemia were found. Of a total of 22 patients who underwent liver biopsy, significant iron deposition was found in one patient. Fifteen patients underwent C282Y and H63D genotyping, with two cases of H63D heterozygosity. Fourteen patients had first-degree relatives with hyperferritinemia. Three families were identified with more than two members affected, which is suggestive of a possible hereditary hyperferritinemia syndrome. CONCLUSION Secondary causes of elevated ferritin in the Asian population, particularly liver disease, are common, but primary iron overload syndromes appear to be rare. In a significant proportion of patients, the etiology remains unexplained. The genetic basis for hyperferritinemia in Asians is poorly defined and requires further study.

Post-menopausal Surrogate Motherhood: A Case Report

Abstract A 58-year-old post-menopausal women was a surrogate mother. She developed severe pre-eclampsia at 35 weeks of pregnancy and was delivered by Caesarean section. Postmenopausal motherhood is a controversial subject. The risk of obstetrical complications (gestational hypertension and diabetes) is high in women over 50. Their care is complex and should be multidisciplinary.