THE UPS AND DOWNS OF PLATELETS Dr Tung Moon Ley Associate - PowerPoint PPT Presentation

THE UPS AND DOWNS OF PLATELETS Dr Tung Moon Ley Associate Consultant Department of Haematology-Oncology

OVERVIEW • INTRODUCTION • GENERAL APPROACH TO CYTOPAENIAS • THROMBOCYTOSIS • THROMBOCYTOPAENIAS

INTRODUCTION • Referrals from Primary Care Physicians make up a large percentage of the referrals to NCIS Haematology Division  Please let patients know that they will be coming to a ‘Cancer Centre’ at the Medical Centre Level 10, NUH • Usually haematological conditions are picked up in 2 ways:  Incidentally – Patient are asymptomatic  In a symptomatic patient

GENERAL APPROACH TO CYTOPAENIAS • Consider the circumstance that the cytopaenias were detected  Was the FBC taken during an acute illness? • History taking paramount  Was there a previous FBC in the past and what was the trend of the counts? • Physical examination  Any abnormal signs which may give a clue to the underlying cause ?  Any physical signs as a result of the cytopaenia? • Initial laboratory tests • Specific laboratory tests

THROMBOCYTOSIS

Where do you start? • Review patients medical history  Any recent surgery/ trauma/ infection?  Duration of thrombocytosis  Degree of thrombocytosis is a poor discriminator between reactive thrombocytosis vs primary thrombocytosis ( reactive causes can lead to a platelet count of >1000 X 10 9 /L at times) • Physical examination  Any thrombo-haemorrhagic signs/ symptoms?  Any hepatosplenomegaly which may suggest a malignant cause? • Initial laboratory testing  FBC, peripheral blood film, serum ferritin (to exclude iron deficiency anaemia), CRP/ ESR (to exclude inflammatory cause)

When to refer to Haematology? • When the platelet count is persistently > 450 X 10 9 /L • Abnormal peripheral blood film findings  Presence of blasts  Leukoerythroblastic picture  Abnormal platelet morphology – hypogranular forms, anisocytosis • Abnormal physical findings such as hepatosplenomegaly • No evidence of iron deficiency • Reactive causes have been excluded

Peripheral blood film findings

Leukoerythroblastic blood film

Differential diagnoses BJH, Guideline for investigation and management of adults and children presenting with thrombocytosis , 2010, 149, 352-375

BCSH Guideline on diagnostic pathway for thrombocytosis, 2013

Case study 1 • 55 year old Malay gentleman who was referred from the Orthopaedic department for leucocytosis and thrombocytosis • Recent left total knee replacement surgery done on the 7 th of October 2013 which was complicated by pyoderma gangrenosum requiring multiple wound debridement and surgeries • Pre op FBC: Normal counts • 19 days post surgery ( peak of his thrombocytosis): TWC 18.86 X 10 9 /L Hb 9.4 g/dL, MCV 87.5 fL, Platelet 843 X 10 9 /L • ESR 101 mm/hr • CRP 30 mg/L

What is the likely diagnosis? • Reactive thrombocytosis? • Primary thrombocytosis? • Others?

Further progress • Impression: Likely reactive thrombocytosis secondary to surgery/ infection • Follow up: Regular monitoring with FBC trend, required 2 months before platelet counts normalised

Case study 2 • 55 year old Chinese lady with a past medical history of a benign thyroid nodule and stress related headaches • Referred by polyclinic for persistent thrombocytosis • Initial FBC done during her annual health check showed a platelet count of 602 X 10 9 /L • A repeat FBC was done during her neurology outpatient visit which showed a platelet count of 544 X 10 9 /L • In February 2017, she had another FBC done at a private clinic which showed a platelet count of 569 X 10 9 /L ( TWC and Hb normal) • In clinic, her labs were: • TWC 7.98 X 10 9 /L, Hb 13.5 g/dL MCV 93.1 fL, Platelet 596 X 10 9 /L • pBF: Occasional large platelet, otherwise NAD • Ferritin 138 ug/L, CRP< 5 mg/L

What is the likely diagnosis? • Reactive thrombocytosis? • Primary thrombocytosis? • Others?

Further progress • Mutational tests: JAK2 V617F mutation present, CALR/ MPL negative • Final diagnosis: JAK2 positive Essential Thrombocythaemia • Treatment: Aspirin, no cytoreduction required as she is considered intermediate risk

THROMBOCYTOPAENIAS

Where do you start? • Review patients medical history  Any recent illness/ new drug used?  Duration of thrombocytopaenia  Degree of thrombocytopaenia is crucial  Drug history – including changes in dosage/ new drugs started • Physical examination  Any bleeding manifestations?  Any hepatosplenomegaly which may suggest a malignant cause? • Initial laboratory testing  FBC  Peripheral blood film – exclude a spurious cause of thrombocytopaenia due to EDTA induced platelet clumping, exclude presence of any abnormal white cells, look for presence of schistocytes to exclude thrombotic thrombocytopaenia purpura (TTP) which is a medical emergency  Other tests based on differential diagnoses – LFT, viral serologies, autoimmune screen, etc

When should you refer to Haematology? • Patients develops bleeding symptoms ( regardless of absolute platelet counts) • Platelet count is downward trending ( with or without symptoms) • Patient develops other cytopaenias (leukopaenia, neutropaenia, anaemia) • Patient develops symptoms which may be linked to an associated condition  E.g TTP – fever, fluctuating neurological deficits, renal impairment, microangiopathic haemolytic anaemia, thrombocytopaenia • Unexplained thrombocytopaenia despite investigations

Tefferi, Mayo Clin.Proc, July 2005

Stasi, How to approach thrombocytopenia, Hematology 2012

Stasi, How to approach thrombocytopenia, Hematology 2012

What do haematologist do in the clinic? History Physical • Bleeding symptoms/history • Bleeding foci • Recent URTI • Rash • Recent vaccination • Chronic liver disease stigmata • Recent travel • Hepatomegaly • Medications and OTC • Splenomegaly • Previous blood counts • • Family history Lymphadenopathy • Autoimmune symptoms • Neurologic • Fever/wt loss/night sweats • Alcohol • HIV/Hep B/C risk factors • History of liver disease

Initial laboratory tests Where indicated, based Mandatory • on suspicion FBC • Blood film • Lupus anticoagulant • PT/APTT • Anti-dsDNA and Anti- • B12/folate ENA • Liver function • US HBS • Creatinine • HIV test • Bone marrow • HBsAg • VWD screen / Platelet • Anti-HCV function tests / family • ANA screen

Case study 1 • 57 year old Chinese lady • Referred from IMH for mild thrombocytopaenia (plt 156 10 9 /L) in November 2012 • FBC showed: TWC 4.81 X 10 9 /L, Hb 14 g/dL, Platelet 139 X 10 9 /L • pBF: NAD • Renal panel/ LFT normal, LDH 588 U/L ( mildly elevated) • Reviewed in clinic in Dec 2012: Platelet dropped to 90 X10 9 /L, ANC 1.10 X 10 9 /L,Hb 12.9 g/dL • 1 month later at her Haem TCU: TWC 2.50 X 10 9 /L ,Hb 9.9 g/dL, MCV 85.9 fL, Platelet 67x10 9 /L, ANC 0.65 X 10 9 /L, Blasts of 2% seen on peripheral blood

What is the likely diagnosis? • Spurious? • Drug-induced? • TTP/HUS? • Primary bone marrow disorder? • ITP?

Further progress • Patient underwent a bone marrow assessment • Diagnosed as a Philadelphia positive B cell Acute Lymphoblastic Leukaemia • Underwent chemotherapy followed by an allogeneic stem cell transplant in August 2013 • Currently still in remission and well

Case study 2 • 50-year-old male presents to ED with 1-day history of vomiting and headache. He was noted by family members to be confused and later the same evening, found slumped on the floor. Patient had been unwell and noted to be jaundiced since returning from holiday in Batam 2 days ago. Patient has no past medical history of note. • On examination, vital signs were: Temp 38.0 o C, BP 190/100, HR 123, SpO2 100% on NRM. • Neurologic examination reveals a combative patient, fluctuating conscious level and intermittent left gaze preference. There is bruising on limbs and petechiae on limbs and trunk. Cardiorespiratory and abdominal examinations are unremarkable. Jaundice is noted. • Blood sugar level is 7.0mmol/l. • The patient was soon noted to have declining GCS to 7 and unresponsive and was intubated for airway protection

What is the likely diagnosis? • Spurious? • Drug-induced? • TTP/HUS? • Primary bone marrow disorder? • ITP?

Further progress • Diagnosis: TTP • Started on plasma exchange

What is TTP? • TTP is thrombotic thrombocytopenic purpura • Serious and potentially fatal disease • Without treatment, 90% mortality • With plasma exchange, survival is 80% • Early deaths can occur: approximately half of deaths occur within the first 24 hours • Rare disease; 6 per million per year

How is TTP diagnosed? • Classic clinical pentad of : • Microangiopathic haemolytic anaemia (MAHA) • Thrombocytopaenia, • Fever, • Renal failure, • Neurological signs (fluctuating) • Most cases do not have the full pentad • Renal failure and fever may not be prominent • MAHA and thrombocytopenia alone without any other cause is sufficient for the diagnosis