Post on 25-Dec-2019
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 109/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 109/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 7th 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 109/L Hb 9.4 g/dL, MCV 87.5 fL, Platelet 843 X 109/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 109/L • A repeat FBC was done during her neurology outpatient
visit which showed a platelet count of 544 X 109/L • In February 2017, she had another FBC done at a private
clinic which showed a platelet count of 569 X 109/L ( TWC and Hb normal)
• In clinic, her labs were:
• TWC 7.98 X 109/L, Hb 13.5 g/dL MCV 93.1 fL, Platelet 596 X 109/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
• Bleeding symptoms/history
• Recent URTI
• Recent vaccination
• Recent travel
• Medications and OTC
• Previous blood counts
• Family history
• Autoimmune symptoms
• Fever/wt loss/night sweats
• Alcohol
• HIV/Hep B/C risk factors
• History of liver disease
Physical
• Bleeding foci
• Rash
• Chronic liver disease stigmata
• Hepatomegaly
• Splenomegaly
• Lymphadenopathy
• Neurologic
Initial laboratory tests
Mandatory
• FBC
• Blood film
• PT/APTT
• B12/folate
• Liver function
• Creatinine
• HIV test
• HBsAg
• Anti-HCV
• ANA
Where indicated, based
on suspicion
• Lupus anticoagulant
• Anti-dsDNA and Anti-
ENA
• US HBS
• Bone marrow
• VWD screen / Platelet
function tests / family
screen
Case study 1
• 57 year old Chinese lady
• Referred from IMH for mild thrombocytopaenia (plt 156 109/L)
in November 2012
• FBC showed: TWC 4.81 X 109/L, Hb 14 g/dL, Platelet 139 X
109/L
• pBF: NAD
• Renal panel/ LFT normal, LDH 588 U/L ( mildly elevated)
• Reviewed in clinic in Dec 2012:
Platelet dropped to 90 X109/L, ANC 1.10 X 109/L,Hb 12.9 g/dL
• 1 month later at her Haem TCU:
TWC 2.50 X 109/L ,Hb 9.9 g/dL, MCV 85.9 fL,
Platelet 67x109/L, ANC 0.65 X 109/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 38.0oC, 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
What is MAHA?
• MAHA = microangiopathic hemolytic anemia
• Diagnosis on the blood film
• Red cell fragments, schistocytes
• With evidence of hemolysis: • Reticulocytosis,
• Unconjugated bilirubinemia,
• Elevated lactate dehydrogenase
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What other clinical presentations of TTP are
there?
Presenting clinical features and signs in acute TTP
Thrombocytopenia Epistaxis, bruising, petechiae, hematuria, menorrhagia, GI bleeding, retinal hemorrhage
Central nervous system Often flitting and variable, present in 70-80% Confusion, headache, paresis, aphasia, dysarthria, visual. Overt cerebral infarcts. In rare cases, neurology precedes MAHA/ thrombocytopenia by weeks
Non-specific Pallor, jaundice, fatigue, arthralgia/myalgia
Renal impairment Usually not prominent, proteinuria, microhematuria
Cardiac Myocardial infarct, chest pain, hypertension, heart failure
Gastrointestinal Abdominal pain, vomiting, diarrhoea, pancreatitis
ANY QUESTIONS?
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Thank you for your attention
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