Clinical characteristics and outcomes of thrombotic microangiopathy in Malaysia

Yee Yee Yap,Jameela Sathar,Kian Boon Law,Putri Astina Binti Zulkurnain,Syed Carlo Edmund,Kian Meng Chang,Ross Baker 대한혈액학회 2018 Blood Research Vol.53 No.2

Background Thrombotic microangiopathy (TMA) with non-deficient ADAMTS-13 (a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13) outcome is unknown hence the survival analysis correlating with ADAMTS-13 activity is conducted in Malaysia/ Methods This was a retrospective epidemiological study involving all cases of TMA from 2012‒2016. Results We evaluated 243 patients with a median age of 34.2 years; 57.6% were female. Majority of the patients were Malay (62.5%), followed by Chinese (23.5%) and Indian (8.6%). The proportion of patients with thrombotic thrombocytopenic purpura (TTP) was 20.9%, 72.2% of which were acquired while 27.8% were congenital. Patients with ADAMTS-13 activity ≥5% had a four-fold higher odds of mortality compared to those with ADAMTS-13 activity <5% (odds ratio: 4.133, P=0.0425). The mortality rate was 22.6% (N=55). Most cases had secondary etiologies (42.5%), followed by acquired TTP (16.6%), atypical hemolytic uremic syndrome (HUS) or HUS (12.8%) and congenital TTP (6.4%). Patients with secondary TMA had inferior overall survival (P=0.0387). The secondary causes comprised systemic lupus erythematosus (30%), infection (29%), pregnancy (10%), transplant (8%), malignancy (6%), and drugs (3%). Transplant-associated TMA had the worst OS (P=0.0016) among the secondary causes. Plasma exchange, methyl-prednisolone and intravenous immunoglobulin were recorded as first-line treatments in 162 patients, while rituximab, bortezomib, vincristine, azathioprine, cyclo-phosphamide, cyclosporine, and tacrolimus were described in 78 patients as second-line treatment. Conclusion This study showed that TMA without ADAMTS-13 deficiency yielded inferior outcomes compared to TMA with severeADAMTS-13 deficiency, although this difference was not statistically significant.

Blood management strategies in congenital Glanzmann thrombasthenia at a hematology referral center

Ganesh Kasinathan,Jameela Sathar 대한혈액학회 2021 Blood Research Vol.56 No.4

Background Glanzmann thrombasthenia is associated with abnormalities in the glycoprotein IIb/IIIa receptor. This study, conducted at Ampang Hospital, Malaysia, aimed to assess outcomes of blood management strategies for Glanzmann thrombasthenia. Methods Ten patients with Glanzmann thrombasthenia aged 9 years (2009‒2018) were examined. Data on clinical characteristics, transfusion practices, and patient blood management were obtained from medical records. Patient blood management methods included parenteral iron, erythropoietin, hormonal pills, intrauterine progesterone contraceptive devices, tranexamic acid, and recombinant factor VIIa. Primary outcomes were hemoglobin levels and the proportion of patients who received blood transfusion. Secondary outcomes were morbidity and mortality. Results The median age at diagnosis was 8.2 years (range, 1‒15 yr). The female-to-male ratio was 9:1. Eight patients had type 2 disease (5‒20% of normal GPIIb/IIIa), and two patients had type 1 disease (normal GPIIb/IIIa <5%). All patients had iron deficiency. All female patients presented with significant menorrhagia. Other bleeding symptoms included epistaxis, spontaneous skin bruising, hemoptysis, gingival bleeding, knee hemarthrosis, and pelvic hematoma. No patient experienced life-threatening bleeding. Our patients had a mean hemoglobin level of 5.6 g/dL at diagnosis. All patients were optimized using non-transfusion methods as described above. Our patient had a current mean hemoglobin level of 11 g/dL. Approximately 70% (7/10) of patients did not experience receiving blood transfusions in the last 5 years. No patient experienced non-transfusion-related morbidities such as sepsis, thromboembolism, or cardiorespiratory events. Conclusion High cost, transfusion-related adverse events, and immunomodulation could be effectively prevented by avoiding unnecessary blood transfusions.

Clinical characteristics and outcomes of thrombotic microangiopathy in Malaysia

Yee Yee Yap,Jameela Sathar,Kian Boon Law,Putri Astina Binti Zulkurnain,Syed Carlo Edmund,Kian Meng Chang,Ross Baker 대한혈액학회 2018 Blood Research Vol.53 No.2

Background Thrombotic microangiopathy (TMA) with non-deficient ADAMTS-13 (a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13) outcome is unknown hence the survival analysis correlating with ADAMTS-13 activity is conducted in Malaysia/ Methods This was a retrospective epidemiological study involving all cases of TMA from 2012‒2016. Results We evaluated 243 patients with a median age of 34.2 years; 57.6% were female. Majority of the patients were Malay (62.5%), followed by Chinese (23.5%) and Indian (8.6%). The proportion of patients with thrombotic thrombocytopenic purpura (TTP) was 20.9%, 72.2% of which were acquired while 27.8% were congenital. Patients with ADAMTS-13 activity ≥5% had a four-fold higher odds of mortality compared to those with ADAMTS-13 activity <5% (odds ratio: 4.133, P=0.0425). The mortality rate was 22.6% (N=55). Most cases had secondary etiologies (42.5%), followed by acquired TTP (16.6%), atypical hemolytic uremic syndrome (HUS) or HUS (12.8%) and congenital TTP (6.4%). Patients with secondary TMA had inferior overall survival (P=0.0387). The secondary causes comprised systemic lupus erythematosus (30%), infection (29%), pregnancy (10%), transplant (8%), malignancy (6%), and drugs (3%). Transplant-associated TMA had the worst OS (P=0.0016) among the secondary causes. Plasma exchange, methyl-prednisolone and intravenous immunoglobulin were recorded as first-line treatments in 162 patients, while rituximab, bortezomib, vincristine, azathioprine, cyclo-phosphamide, cyclosporine, and tacrolimus were described in 78 patients as second-line treatment. Conclusion This study showed that TMA without ADAMTS-13 deficiency yielded inferior outcomes compared to TMA with severeADAMTS-13 deficiency, although this difference was not statistically significant.

Philadelphia-positive (PH+) acute lymphoblastic leukemia (ALL): developing strategies for curing this stubborn disease

Christopher Chin Keong Liam,Yang Liang Boo,Siew Lian Chong,Jameela Sathar,Tee Chuan Ong,Sen Mui Tan 대한혈액학회 2022 Blood Research Vol.57 No.2

Validating lactate dehydrogenase (LDH) as a component of the PLASMIC predictive tool (PLASMIC-LDH)

Christopher Chin Keong Liam,Jim Yu-Hsiang Tiao,Yee Yee Yap,Yi Lin Lee,Jameela Sathar,Simon McRae,Amanda Davis,Jennifer Curnow,Robert Bird,Philip Choi,Pantep Angchaisuksiri,Sim Leng Tien,Joyce Ching Me 대한혈액학회 2023 Blood Research Vol.58 No.1

Background The PLASMIC score is a convenient tool for predicting ADAMTS13 activity of <10%. Lactate dehydrogenase (LDH) is widely used as a marker of haemolysis in thrombotic thrombocytopenic purpura (TTP) monitoring, and could be used as a replacement marker for lysis. We aimed to validate the PLASMIC score in a multi-centre Asia Pacific region, and to explore whether LDH could be used as a replacement marker for lysis. Methods Records of patients with thrombotic microangiopathy (TMA) were reviewed. Patients’ ADAMTS13 activity levels were obtained, along with clinical/laboratory findings relevant to the PLASMIC score. Both PLASMIC scores and PLASMIC-LDH scores, in which LDH replaced traditional lysis markers, were calculated. We generated a receiver operator characteristics (ROC) curve and compared the area under the curve values (AUC) to determine the predictive ability of each score. Results 46 patients fulfilled the inclusion criteria, of which 34 had ADAMTS13 activity levels of <10%. When the patients were divided into intermediate-to-high risk (scores 5‒7) and low risk (scores 0‒4), the PLASMIC score showed a sensitivity of 97.1% and specificity of 58.3%, with a positive predictive value (PPV) of 86.8% and negative predictive value (NPV) of 87.5%. The PLASMIC-LDH score had a sensitivity of 97.1% and specificity of 33.3%, with a PPV of 80.5% and NPV of 80.0%. Conclusion Our study validated the utility of the PLASMIC score, and demonstrated PLASMIC-LDH as a reasonable alternative in the absence of traditional lysis markers, to help identify high-risk patients for treatment via plasma exchange.