A case of oxaliplatin-induced immune-mediated thrombocytopenia

Oxaliplatin is a platinum compound used in patients with gastrointestinal malignancies. It is known to evoke a drug-induced immune-mediated thrombocytopenia, which has not been reported in Korea. We describe a 53-year-old man who developed oxaliplatin-induced immune-mediated thrombocytopenia during chemotherapy for colon cancer. Oxaliplatin-dependent IgG platelet antibodies were detected in his serum on flow cytometry. He was treated with immunoglobulin and corticosteroids without any complications. Physicians should consider oxaliplatin-induced immune-mediated thrombocytopenia, when a sudden, isolated thrombocytopenia develops during chemotherapy with oxaliplatin.

Prevention of Venous Thromboembolism, 2nd Edition: Korean Society of Thrombosis and Hemostasis Evidence-Based Clinical Practice Guidelines

In 2010, we proposed the first Korean Guidelines for the Prevention of Venous Thromboembolism (VTE). It was applicable to Korean patients, by modifying the contents of the second edition of the Japanese guidelines for the prevention of VTE and the 8th edition of the American College of Chest Physicians (ACCP) evidence-based clinical practice guidelines. From 2007 to 2011, we conducted a nationwide study regarding the incidence of VTE after major surgery using the Health Insurance Review and Assessment Service (HIRA) database. In addition, we have considered the 9th edition of the ACCP Evidenced-Based Clinical Practice Guidelines, published in 2012. It emphasized the importance of clinically relevant events as opposed to asymptomatic outcomes with preferences for both thrombotic and bleeding outcomes. Thus, in the development of the new Korean guidelines, three major points were addressed: 1) the new guidelines stratify patients into 4 risk groups (very low, low, moderate, and high) according to the actual incidence of symptomatic VTE from the HIRA databases; 2) the recommended optimal VTE prophylaxis for each group was modified according to condition-specific thrombotic and bleeding risks; 3) guidelines are intended for general information only, are not medical advice, and do not replace professional medical care and/or physician advice.

Characterization of anti-factor VIII antibody in a patient with acquired hemophilia A

Acquired hemophilia A (AHA) is a bleeding disorder caused by the development of an auto-antibody against endogenous factor VIII (FVIII). In this study, the epitope of the autoantibody was identified in a 67-year-old female patient with AHA. A prolonged activated partial thromboplastin time (77.4 s) that failed to correct in an incubation mixing test (68.2 s), a decreased FVIII activity, and a high FVIII inhibitor (14.6 Bethesda units/mL) were observed. Enzyme-linked immunosorbent assay demonstrated that the antibody belonged to the immunoglobulin G4 subclass. An immunoblotting assay revealed the light chain (A3/C1/C2 domain) of FVIII as the binding region of the antibody. The bleeding experienced by our patient resulted from the interference of FVIII binding to both FIX by anti-A3 antibodies and phospholipids and von Willebrand factor by anti-C2 antibodies. To the best of our knowledge, this is the first study in Korea characterizing an autoantibody in the context of AHA.

Characterization of anti-factor VIII antibody in a patient with acquired hemophilia A

Acquired hemophilia A (AHA) is a bleeding disorder caused by the development of an auto-antibody against endogenous factor VIII (FVIII). In this study, the epitope of the autoantibody was identified in a 67-year-old female patient with AHA. A prolonged activated partial thromboplastin time (77.4 s) that failed to correct in an incubation mixing test (68.2 s), a decreased FVIII activity, and a high FVIII inhibitor (14.6 Bethesda units/mL) were observed. Enzyme-linked immunosorbent assay demonstrated that the antibody belonged to the immunoglobulin G4 subclass. An immunoblotting assay revealed the light chain (A3/C1/C2 domain) of FVIII as the binding region of the antibody. The bleeding experienced by our patient resulted from the interference of FVIII binding to both FIX by anti-A3 antibodies and phospholipids and von Willebrand factor by anti-C2 antibodies. To the best of our knowledge, this is the first study in Korea characterizing an autoantibody in the context of AHA.

A case of transfusion-related acute lung injury induced by anti-human leukocyte antigen antibodies in acute leukemia

Transfusion-related acute lung injury (TRALI) is a noncardiogenic pulmonary edema that occurs during or within 6 hours after transfusion. Risk factors for TRALI, which is relatively common in critically ill patients, include recent surgery, hematologic malignancy, and sepsis. Here, we report a case of TRALI induced by anti-human leukocyte antigen (anti-HLA) class II antibodies (HLA-DR) occurring after transfusion of platelet concentrates in a patient with acute leukemia. Although most patients with TRALI show improvement within 48-96 hours, our patient's condition rapidly worsened, and he did not respond to supportive treatment. TRALI is a relatively common and serious adverse transfusion reaction that requires prompt diagnosis and management.

A Trp33Arg Mutation at Exon 1 of the MYH9 Gene in a Korean Patient with May-Hegglin Anomaly

In this report, we describe a Korean patient with May-Hegglin anomaly from a mutation of the MYH9 gene. The proband was a 21-year-old man with thrombocytopenia. He did not have a bleeding tendency. His neutrophil count was normal at 7490/mm3; however, the neutrophils contained abnormal basophilic inclusions in their cytoplasm. The platelet count was decreased at 15000/mm3 with giant platelets. Coagulation test results were not remarkable. Direct sequencing of MYH9 revealed that he was heterozygous for a mutation in exon 1, which was a 97T>A substitution mutation affecting codon 33, substituting tryptophan with arginine (Trp33Arg). Family study showed that both of his parents had normal phenotype and genotypes, indicating a de novo occurrence of the mutation in the proband.

Health insurance system for hematologic diseases: what should we do?

No abstract available.

Korean Guidelines for the Prevention of Venous Thromboembolism

This guideline focuses on the primary prevention of venous thromboembolism (VTE) in Korea. The guidelines should be individualized and aim at patients scheduled for major surgery, as well as patients with a history of trauma, high-risk pregnancy, cancer, or other severe medical illnesses. Currently, no nation-wide data on the incidence of VTE exist, and randomized controlled trials aiming at the prevention of VTE in Korea have yielded few results. Therefore, these guidelines were based on the second edition of the Japanese Guidelines for the Prevention of VTE and the eighth edition of the American College of Chest Physicians (ACCP) Evidenced-Based Clinical Practice Guidelines. These guidelines establish low-, moderate-, and high-risk groups, and recommend appropriate thromboprophylaxis for each group.

High-dose Immunoglobulin Infusion for Thrombotic Thrombocytopenic Purpura Refractory to Plasma Exchange and Steroid Therapy

The outcomes of the treatment of thrombotic thrombocytopenic purpura (TTP) have been shown to be improved by the administration of plasma exchange. However, treatment options are currently limited for cases refractory to plasma exchange. The autoantibodies that block the activity of ADAMTS13 have been demonstrated to play a role in the pathogenesis of TTP; therefore, high-dose immunoglobulin, which can neutralize these autoantibodies, may be useful for refractory TTP. However, successful treatment with high-dose immunoglobulin for TTP refractory to plasma exchange and corticosteroids has yet to be reported in Korea. Herein, we describe a refractory case which was treated successfully with high-dose immunoglobulin. A 29-year-old male diagnosed with TTP failed to improve after plasma exchange coupled with additional high-dose corticosteroid therapy. As a salvage treatment, we initiated a 7-day regimen of high-dose immunoglobulin (400 mg/kg) infusions, which resulted in a complete remission, lasting up to the last follow-up at 18 months. High-dose immunoglobulin may prove to be a useful treatment for patients refractory to plasma exchange; it may also facilitate recovery and reduce the need for plasma exchange.

ADAMTS13 Activity in Childhood Hemolytic Uremic Syndrome(HUS)

PURPOSE: HUS usually occurs in children after infection with shiga toxin-producing microorganism(D+HUS). In contrast, non-postdiarrheal(D-) HUS occurs at any age and has a high rate of relapse and a poor prognosis. The clinical presentation of D-HUS is similar to that of thrombotic thrombocytopenic purpura(TTP). Recently severe deficiencies of ADAMTS13 were reported not only in TTP and D- HUS but also in D+ HUS during their acute phase. The purpose of the study is to evaluate the plasma ADAMTS13 activity in D+ and D-HUS. METHODS: Nineteen children with HUS(D+ HUS 12 and D- HUS 7) were enrolled. The assays of plasma ADAMTS13 activity were performed during the acute stage in the D+ HUS and at various stages of relapsing courses in the D- HUS patients by multimer assay, based on electrophoresis. RESULTS: The median plasma activity of ADAMTS13 in D+ HUS and D- HUS were 80.9%(37.8-132.4%) and 53.9%(1.0-94.1%), respectively, which were not statistically significantly different from control(86.4%, 34.2-112.3%)(P>0.05). One boy with D- HUS had severe deficiency of ADAMTS13(1.0%). His platelet count was normalized temporarily by fresh frozen plasma infusion. CONCLUSION: We have demonstrated that there is no significant difference of the plasma ADAMTS13 activity between D+ HUS, D- HUS and control. We detected severe deficiency of ADAMTS13 in one boy who presented with relapsing episodes of D- HUS. ADAMTS13 deficiency should be considered in the subgroup of D- HUS especially with early onset and recurrent courses. Plasma therapy can be beneficial in this subgroup.

Clinical Features of Pregnancy and Delivery in Patients with Idiopathic Thrombocytopenic Purpura

BACKGROUND: Patients with the condition of idiopathic thrombocytopenic purpura (ITP) may present with, maternal and fetal hemorrhagic complications. Appropriate monitoring and treatment may be important in obstetric management. METHODS: A retrospective chart review was performed for obstetric patients with ITP at Bundang CHA hospital from March 1996 to March 2005. RESULTS: Nineteen women with ITP delivered 22 children in 22 pregnancies. The median age at delivery was 30 years (range, 21~37 years). The median platelet counts before pregnancy, during pregnancy, and at delivery were 44,000/microliter (range, 20,000~225,000/microliter), 40,500/microliter (range, 13,000~335,000/microliter), and 73,500/microliter (range, 40,000~308,000/microliter. Treatment for ITP was done in 14 cases (63.6%) during pregnancy and in 18 cases (81.8%) at delivery. Platelet transfusion was done for one case during pregnancy but, was performed in 17 cases (77.3%) at delivery. Vaginal delivery was done in 10 cases (45%) and a Cesarean section was done in 12 cases (55%). No obstetric complications were observed. The median platelet count of 17 infants was 220,000/microliter (range, 59,000~315,000/microliter). Four neonates were born with platelet counts below 150,000/microliter. No infant showed any clinical signs of hemorrhage and there were not any neonatal complications. CONCLUSION: In our study, obstetric patients with ITP and their neonates were safe with no hemorrhagic complication. However, when compared to the current guidelines, the treatment strategy used in the present study was excessive. Appropriate treatment according to the guidelines is necessary during the obstetric management of patients with ITP.

A Case of Mantle Cell Lymphoma Treated with Autologous Stem Cell Transplantation and Rituximab

Mantle cell lymphoma is a subtype of aggressive non-Hodgkin's lymphoma and usually presents in advanced stages. When treated with a regimen such as CHOP, the median survival is about three years. More aggressive front-line therapy with the hyper-CVAD regimen or high-dose therapy with stem cell support has shown encouraging results in several trials. The addition of rituximab to the chemotherapy regimens, or high-dose therapy, increased the response and survival rates in patients with mantle cell lymphoma. We report a case of mantle cell lymphoma that was successfully treated with aggressive front-line treatment strategies. The patient achieved complete remission with initial hyper-CVAD regimen, and was consolidated with autologous stem cell transplantation and subsequent rituximab.

Reduced-intensity Umbilical Cord Blood Transplantation in Adult Acute Myeloid Leukemia: Report of Four Cases

The outcome after unrelated cord blood transplantation (CBT) is similar to that of matched unrelated bone marrow transplantation in children, and the results of CBT in adult patients has recently shown improvement. In addition, the use of reduced-intensity conditioning regimens for CBT has shown stable engraftment and reduced treatment-related mortality (TRM). From May 2005 to Jan 2006, four adult patients with acute myelogenous leukemia were treated with CBT after reduced-intensity conditioning at our hospital. The mean age of patients was 53.8 yrs, and all patients received 2 HLA antigen mismatched single unit cord blood. The infused mean cell dose was 2.85 x 10(7)/kg for total nucleated cells and 0.72 x 10(5)/kg for CD34+ cells. All patients had engraftment. The mean number of days to WBC and platelet engraftment was D+20.3 and D+60.3, respectively. There was no TRM within 100 days after transplantation. At the last follow up, three of the four patients were alive. One patient transplanted in first complete remisson is alive in remission at day 413, but the other patients transplanted in advanced disease all relapsed. Reduced-intensity CBT is a feasible approach in selected adult patients with acute myeloid leukemia.

A Case of Acquired Glanzmann's Thrombasthenia

Glanzmann's thrombasthenia (GT) is a rare inherited platelet disorder, which is characterized by a complete lack of platelet aggregation due to a deficiency or abnormality of the membrane glycoprotein IIb/IIIa complex. Anti-GPIIb/IIIa antibodies have also been identified to cause platelet dysfunction in patients with a normal platelet count, but this has only been rarely encountered. The condition is also known as acquired GT. Herein, we describe a patient with acquired GT and a history of Evans' syndrome, who presented with severe bleeding and platelet dysfunction, but with a normal platelet count and GP IIb/IIIa expression.

The Usefulness of the New ADAMTS-13 Activity Assay using a Fluorescence-quenching Substrate for the Diagnosis of Thrombotic Thrombocytopenic Purpura

BACKGROUND: Ever since medical professionals have recognized the important role of ADAMTS-13 in the pathogenesis of TTP, several methods to diagnosis the activity of ADAMTS-13 in the plasma of TTP patients haves been developed. However these assays have not been widely used in practice because they are cumbersome and they require several days to complete. In this study we examine the new, rapid ADAMTS-13 activity assay that uses fluorescence resonance energy transfer and we compared it with the conventional assay to determine its diagnostic advantage. METHODS: Seven TTP patients were compared with 60 healthy controls. The plasma ADAMTS-13 activity was measured using the fluorescence-quenching substrate assay method. The results were compared with the results of performing multimer analysis of SDS-agarose gel electrophoresis. RESULTS: It took only 2 hour to complete the fluorescence-quenching substrate assay. The median ADAMTS-13 activity using the fluorescence-quenching substrate was 5.9% (range: 0~29.9%) for the patient group and 99.1% (range: 74.4~143.3%) for the healthy group, respectively. The median ADAMTS-13 activity using multimer analysis of SDS-agarose gel electrophoresis was 5.6% (range: 1.6~28.8%) for the patients group and 87.7% (range: 44.1~120.9%) for the healthy group, respectively. The ADAMTS-13 activities of the two assays were well correlated (correlation coefficient: 0.69). CONCLUSION: The quantification of ADAMTS-13 activity with using the fluorescence-quenching substrate is rapid and highly specific for the diagnosis of TTP and it is expected to be used widely in the diagnosis of TTP.

Changes of the Activity of ADAMTS-13 in aging, Pregnancy and Disease / 대한혈액학회지

BACKGROUND: ADAMTS-13 is an enzyme that has function of cleaving von Willebrand factor multimer to monomer at normal plasma level. We have previously reported that the activity of ADAMTS-13 is decreased in thrombotic thrombocytopenic purpura (TTP) and advanced malignancy. In this study, we measured ADAMTS-13 activity in aging, pregnancy and other disease conditions for further understanding of its behavior in a variety of conditions. METHODS: The study included among 125 inpatients who were admitted at the Bundang Cha Hospital from July 2003 to February 2004 with liver cirrhosis, chronic renal failure, sepsis, disseminated intravascular coagulopathy (DIC), gastric cancer, colon cancer, and thrombotic microangiopathy, and 100 control subjects of different ages, in 20 normal full-term pregnant women and 20 postpartum women. The activity of ADAMTS-13 was assessed by multimer assay, based on electrophoresis. The presence of inhibitor was evaluated by mixing the plasma of patient with severely deficient ADAMTS-13 activity and normal plasma at the ratio of 1:1, 1:2, and 1:3. RESULTS: The median value, according to the age group from age 20~39 was recorded 97 % (range, 44~108%), age 40~59, 90% (range, 50~109%), and age group over 60 was 79% (range, 44~108%). the median value at third trimester was 76% (range, 6~103%), with postpartum state 84% (range, 74~100%), however, there was no significant difference compared with the healthy adult group. The median value for each categories of disease were 81% (range, 27~94%) for liver cirrhosis (P=0.0049), 61% (range, 25~110%) for chronic renal failure (P=0.0030), 80% (range, 32~111%) for DIC (P=0.0449) and 12% (range, 2~29%) for thrombotic microangiopathy (P<0.0001), respectively, compared to normal. In sepsis, gastric cancer and colon cancer, there was no significant change. In addition, the result showed positive for inhibitor assay among 3 patients out of 5 cancer patients, with severe deficiency of ADAMTS-13 activity. CONCLUSION: There was a decrease in the ADAMTS-13 activity among patients with liver cirrhosis, chronic renal failure, DIC and thrombotic microangiopathy compared with healthy control and inhibitors against ADAMTS-13 was detected in some malignant patients.

Comparison between Diagnostic Criteria for Disseminated Intravascular Coagulation (DIC) of the International Society on Thrombosis and Hemostasis (ISTH) and the Korean Society on Thrombosis and Hemostasis (KSTH) / 대한혈액학회지

BACKGROUND: The criteria set by the International Society on Thrombosis and Hemostasis (ISTH) with the criteria of the Korean Society on Thrombosis and Hemostasis (KSTH) for the diagnosis of DIC was compared to evaluate the agreement between two criteria and the characteristics of each criteria. METHODS: Two hundred ninety-six adult patients with sepsis (57 pneumonia, 75 hepatobiliary and gastrointestinal infection, 25 urinary tract infection, 51 infection associated with malignant diseases and 84 other causes) were studied. The rate of agreement in the diagnosis of DIC by the two diagnostic systems was analyzed. Characteristics of each criteria was also analyzed by the comparison of laboratory criteria. RESULTS: The kappa coefficient and concordance rate, agreement parameters in the diagnosis of DIC by the two diagnostic systems was 0.78 and 89.5%, respectively. The median platelet count was lower and FDP level was higher in the patients diagnosed by ISTH criteria than in patients diagnosed by KSTH criteria. CONCLUSION: The agreement between ISTH and KSTH criteria was significantly high.

A Case of Hairy Cell Leukemia, Variant / 대한혈액학회지

Hairy cell leukemia-variant (HCL-variant) is a rare B-cell disorder of hairy cell leukemia cases. The main features are splenomegaly, lymphocytosis and cytopenias without monocytopenia. Diagnosis is based on the distinctive hairy cell morphology and immunophenotype. Cells from hairy cell leukemia (HCL) and HCL-variant have a distinct immunophenotype which is of a mature but not terminally differentiated activated B-cell. We experienced a case of HCL- variant in a 50-year-old man with marked splenomegaly and skin eruptions. Peripheral blood smear showed abnormal lymphoid cells with cytoplasmic projections. The bone marrow was easily aspirated and showed hypercellularity and diffuse interstitial infiltration of hairy cells. Tartrate-resistant acid phosphatase (TRAP) reactivity was negative in the hairy cells. Immunophenotyping results of lymphoid cells were CD2 (-), CD3 (-), CD5 (-), CD7 (-), CD10 (-), CD19 (++), CD20 (+++), sKappa (-), sLambda (+), CD23 (-), CD25 (-), FMC7 (+) and CD103 (++).

A Case of Trichosporon beigelii Fungemia Treated with Amphotericin B and Fluconazole in a Patient with Acute Myelogenous Leukemia / 대한혈액학회지

Trichosporon beigelii is a causative agent of white piedra, an superficial hair shaft infection in immunocompetent individuals, and rarely of disseminated trichosporonosis in immunocompromised patients especially in neutropenic patients with leukemia. Trichosporon infections in immunocompromised patients are frequently fatal despite therapy with amphotericin B. We describe an acute myelogenous leukemia patient with T. beigelii fungemia after remission induction chemotherapy who was successfully treated with amphotericin B and fluconazole.