Usefulness of platelet indices in differentiating thrombocytopenia with and without bone marrow megakaryocytosis.

Introduction
In evaluating the mechanism of thrombocytopenia, it is necessary to know which is more dominant, hypoproductive thrombocytopenia or hyper-destructive thrombocytopenia. For this purpose, bone marrow aspiration, plateletassociated immunoglobulin G (PAIgG), and molecular markers for disseminated intravascular coagulation (DIC) are often evaluated. Bone marrow aspiration provides information about platelet production, such as the number of megakaryocytes and the degree of platelet production, while PAIgG identies the presence of anti-platelet antibodies that lead to platelet destruction.

 Bone marrow examination, which is an invasive test, is necessary for aplastic anaemia (AA), but there is no agreed consensus regarding its necessity for immune thrombocytopenia (ITP) PAIgG is often elevated in ITP, but it is not specic to ITP and an increased PAIgG level is often found in many other diseases. In fact, the necessity for both bone marrow aspiration and PAIgG in ITP was not accepted in the recent guidelines (British Committee for Standards in Haematology General Haematology Task Force, 2003).

 However, these two diagnostic approaches are actually overused in the diagnosis of ITP. Recent advances in automated blood cell analysers have made it possible to measure various blood cell parameters automatically. Among these parameters, platelet indices, such as mean platelet volume (MPV), platelet size deviation width (PDW), and platelet large cell ratio (P-LCR), provide some important information but are not accepted for routine clinical use.

 If these indices really are informative regarding platelet kinetics, they might become very useful laboratory measures for thrombocytopenia. This study will investigate the significance of these platelet indices in the diagnosis of thrombocytopenia associated with increased bone marrow megakaryopoiesis by comparing the levels in hypo- or normoproductive conditions and in hyper-productive thrombocytopenia. As Immune thrombocytopenia is the commonest cause of hyper-destructive thrombocytopenia and also the commonest cause of thrombocytopenia in clinical settings, any usefulness of platelet indices in investigating thrombocytopenia with bone marrow megakaryocytosis can be attributed to ITP as well.

 The sensitivity and specicity of platelet indices to enable the diagnosis of hyperdestructive thrombocytopenia will be evaluated in this study.

Objectives
General Objective:
To assess the usefulness of platelet indices in the investigation of thrombocytopenia Specific objectives:
To study the pattern of platelet indices in cases with increased, normal and decreased megakaryocytes in the bone marrow. To find out any variation in platelet indices relative to age, sex or any other clinical attribute.

Literature Review-1 Platelet size deviation width, platelet large cell ratio, and mean platelet volume have sufcient sensitivity and specicity in the diagnosis of immune thrombocytopenia

Author and Publication

Ken Kaito,1 Hiroko Otsubo, 2 Noriko Usui, 2 Miyuki Yoshida, 1 Jyunko Tanno,1 Etsuko Kurihara, 1 Kozue Matsumoto,1 Ryuzo Hirata, 1 Kenichi Domitsu 1 and Masayuki Kobayashi 2

Study Objective and Design

Objective : to study the significance of MPV, PDW and P-LCR in the diagnosis of thrombocytopenia by comparing the levels in hypo-productive (AA) and hyper-destructive thrombocytopenia (ITP).

Conclusion
These indices could help to distinguish hyper-destructive thrombocytopenia and hypo-productive thrombocytopenia very easily. Platelet indices, if reported, provide a lot of clinical information about the underlying conditions of thrombocytopenia. More attention should be paid to these indices for the diagnosis of thrombocytopenia.

1Central Clinical Laboratory, Jikei University Hospital, and Design: 2Division of Hematology and Prospective study Oncology, Department of Internal Medicine, Jikei University, School of Medicine, Tokyo, Japan British Journal of Haematology , 128, Feb2005

Literature Review-2 Immature Platelet Count: A Simple Parameter for Distinguishing Thrombocytopenia in Pediatric Acute Lymphocytic Leukemia From Immune Thrombocytopenia

Author and Publication

Gabriele Strau, MD , 1 Cora Volle rt, 1 Ar end von Stacke lberg , MD ,2 Andr eas Weimann, MD , 3 Ger hard Gaedick e, MD , 1 and Harald Schu lze, PhD 1 * Berlin Pediatric Blood Cancer 2011;57:641647

Study Objective and Design

Objective : to study whether immature platelet count can be of use in distinguishing thrombocytopenia in pediatric ALL from ITP

Conclusion
IPF% is a useful parameter for dening thrombocytopenia resulting from defective platelet production while the absolute IPF number (IPF#) has the potential to distinguish acute ITP from thrombocytopenia due to diagnosed ALL in children.

Design: Prospective study

Literature Review-3 The Automated Complete Blood Cell Count: Use of the Red Blood Cell Volume Distribution Width and Mean Platelet Volume in Evaluating Anemia and Thrombocytopenia

Author and Publication

Anand Karnad, MD; Thomas R. Poskitt, MD
Hematology-Oncology Section, Veterans Administration Medical Center (Dr Poskitt), and the Departments of Internal Medicine (Drs Poskitt and Karnad) and Pathology (Dr Poskitt), Quillen-Dishner College of Medicine, East Tennessee State University, Johnson City. Arch Intern Med. July 1985;145(7)

Study Objective and Design

Conclusion
.

Inclusion Criteria All cases of thrombocytopenia that undergo bone marrow aspiration study

Exclusion criteria Cases where platelet indices are not available.

Methodology
Study design: Prospective study.
Correlation between the bone marrow megakaryocyte count and the three platelet indices.

Setting: Pathology department, Hemato-pathology section. Duration: one year. Approval by the INSTITUTIONAL REVIEW BOARD & THE ETHICAL COMMITTEE ON RESEARCH,TUTH,IOM. Sample Size: All cases undergoing BM aspiration for thrombocytopenia during one year period.

Diagnosis of ITP
First, the clinician has to determine that there are no blood abnormalities other than low platelet count, and no physical signs except for signs of bleeding. Then, the secondary causes (usually 510 percent of suspected ITP cases) should be excluded. Secondary causes could be leukemia, medications (e.g., quinine, heparin), lupus erythematosus, cirrhosis, HIV,hepatitis C, congenital causes, antiphospholipid syndrome, von Willebrand factor deficiency, onyalai and others.[9][2]

Investigations for Aplastic Anemia

1. FBC and reticulocyte count

2. Blood film examination

3. HbF% in children 4. Bone marrow aspirate and trephine biopsy, including cytogenetics 5. Peripheral blood cytogenetics to exclude Fanconi's anaemia if <35 years old 6. Ham test and/or flow cytometry for PIG-anchored proteins 7. Urine haemosiderin if Ham test positive or PIG-anchored protein deficiency 8. Vitamin B12 and folate 9. Liver function tests 10. Viral studies: hepatitis A, B, C; EBV; CMV

11. Anti-nuclear antibody and anti-dsDNA

12. Chest X-ray 13. Abdominal ultrasound scan