ThrombocytopeniaThrombocytopenia

Dr S W BokhariDr S W Bokhari

Consultant HaematologistConsultant Haematologist

University Hospital Coventry and University Hospital Coventry and WarwickshireWarwickshire

ThrombocytopeniaThrombocytopenia

You are the Surgical HO asked to clerk patient on You are the Surgical HO asked to clerk patient on ward pre-operatively prior to hernia repair.ward pre-operatively prior to hernia repair.

You notice from results on CRRS that his platelet You notice from results on CRRS that his platelet count one week earlier was 25. No previous results.count one week earlier was 25. No previous results.

How do you approach this problem?How do you approach this problem?

Repeat FBCRepeat FBC

Hb 13g/dL WCC 8 Neuts 2.5 Plts 28 MCV 102Hb 13g/dL WCC 8 Neuts 2.5 Plts 28 MCV 102

Ask for blood film to be reviewedAsk for blood film to be reviewed

Film commentFilm comment – confirmed thrombocytopenia, – confirmed thrombocytopenia, normalnormal

platelet morphology; mild macrocytosis; no other platelet morphology; mild macrocytosis; no other abnormalabnormal

featuresfeatures

Inform surgeons/theatres etcInform surgeons/theatres etc

Peripheral blood filmPeripheral blood film

Platelet clumpingPlatelet clumping

HistoryHistory

40 year old man40 year old man

Symptoms:Symptoms:

Bleeding history – severity and durationBleeding history – severity and duration

Recent illness – including infections esp. viralRecent illness – including infections esp. viral

Patient had noticed easy bruising for previous 2 Patient had noticed easy bruising for previous 2 months.months.

Fit and well with no recent illnessFit and well with no recent illness

Mucosal bleeding

Purpura

Past Medical HistoryPast Medical History

Infections – bacterial, viral, fungalInfections – bacterial, viral, fungal Autoimmune diseaseAutoimmune disease Liver diseaseLiver disease MalignancyMalignancy

Occasional backpainOccasional backpain

Road traffic accident 5 years ago following which heRoad traffic accident 5 years ago following which he

received blood transfusionreceived blood transfusion

Family HistoryFamily History

Congenital causes of thrombocytopeniaCongenital causes of thrombocytopenia Autoimmune diseaseAutoimmune disease

Mother – IDDMMother – IDDM

Sister recently diagnosed with SLESister recently diagnosed with SLE

Drug HistoryDrug History

Long list to consider!Long list to consider!

-immune-mediated-immune-mediated

-direct effect on BM or MK-direct effect on BM or MK

Alcohol intakeAlcohol intake

Takes diclofenac for backpainTakes diclofenac for backpain

30 units alcohol per week – spirits30 units alcohol per week – spirits

Smokes 15/daySmokes 15/day

Social HistorySocial History

Occupation - ? Exposure to toxic agentsOccupation - ? Exposure to toxic agents Dietary historyDietary history Recent travel abroad – infectionsRecent travel abroad – infections Risk factors for HIVRisk factors for HIV

Recently made redundant having previously worked Recently made redundant having previously worked inin

motor industrymotor industry

No recent travel abroadNo recent travel abroad

No risk factors for HIVNo risk factors for HIV

ExaminationExamination

Bleeding/bruisingBleeding/bruising AnaemiaAnaemia Clubbing/jaundice (other features of CLD)Clubbing/jaundice (other features of CLD) LymphadenopathyLymphadenopathy Signs of malignancySigns of malignancy HepatomegalyHepatomegaly SplenomegalySplenomegaly

Features associated with congenital causes esp. Features associated with congenital causes esp. FanconiFanconi

anaemiaanaemia

Bruising over arms and legsBruising over arms and legs

? Yellow sclera? Yellow sclera

Liver palpable 3cmLiver palpable 3cm

No other findingsNo other findings

InvestigationsInvestigations

FBCFBC

Pancytopenia or isolated thrombocytopeniaPancytopenia or isolated thrombocytopenia

MCVMCV

Blood filmBlood film

Confirm thrombocytopeniaConfirm thrombocytopenia

Platelet size and morphologyPlatelet size and morphology

Red cell fragmentsRed cell fragments

Red cell abnormalities e.g. target cellsRed cell abnormalities e.g. target cells

WBC featuresWBC features

Giant plateletsGiant platelets

Red cell fragmentsRed cell fragments

Target cellsTarget cells

Hypersegmented neutrophilHypersegmented neutrophil

Hb 13g/dL WCC 5 Neuts 2.0 Plts 28 MCV 102Hb 13g/dL WCC 5 Neuts 2.0 Plts 28 MCV 102

Target cells and stomatocytesTarget cells and stomatocytes

Renal functionRenal function Liver functionLiver function

B12 and folateB12 and folate

Full clotting screenFull clotting screen

Normal renal functionNormal renal function

AST 160 Alk phos 170 ALT 130 Bili 60 AST 160 Alk phos 170 ALT 130 Bili 60 γγGT 100GT 100

B12 110 Folate 1.4B12 110 Folate 1.4

PT ratio 1.6 APTT ratio 1.4 Normal fibrinogen and TTPT ratio 1.6 APTT ratio 1.4 Normal fibrinogen and TT

Autoantibody screen + specific autoantibodies as Autoantibody screen + specific autoantibodies as indicatedindicated

Antiphospholipid antibodiesAntiphospholipid antibodies

Lupus anticoagulantLupus anticoagulant

Anticardiolipin antibodiesAnticardiolipin antibodies

Autoantibodies screen negativeAutoantibodies screen negative

Antiphospholipid antibodies positiveAntiphospholipid antibodies positive

Virology testingVirology testing

EBV, CMV, toxoplasmaEBV, CMV, toxoplasma

Hep B, CHep B, C

HIVHIV

Hepatitis C positiveHepatitis C positive

Presumed secondary to blood transfusionPresumed secondary to blood transfusion

Causes of thrombocytopeniaCauses of thrombocytopenia

Failure of productionFailure of production

Increased consumption/destructionIncreased consumption/destruction

Abnormal pooling - splenomegalyAbnormal pooling - splenomegaly

Failure of productionFailure of production

Congenital:Congenital:

Fanconi anaemia, TAR (thrombocytopenia with absentFanconi anaemia, TAR (thrombocytopenia with absent

radii), Wiskott-Aldrich syndrome, Bernard-Soulier radii), Wiskott-Aldrich syndrome, Bernard-Soulier synd.*,synd.*,

May-Hegglin anomaly*, Alport synd. variant*, Grey May-Hegglin anomaly*, Alport synd. variant*, Grey plateletplatelet

synd.*synd.*

Acquired:Acquired: – specific thrombocytopenia – specific thrombocytopenia

Infection esp. viral Infection esp. viral

Nutritional deficiency – B12/folateNutritional deficiency – B12/folate

Toxic effect of drugs (more often immune) or alcoholToxic effect of drugs (more often immune) or alcohol

Failure of productionFailure of production

Acquired: Acquired: – as part of bone marrow failure– as part of bone marrow failure

Drugs including chemotherapyDrugs including chemotherapy

RadiotherapyRadiotherapy

Marrow infiltration – malignant/non-malignantMarrow infiltration – malignant/non-malignant

Aplastic anaemiaAplastic anaemia

Bone marrow aspirateBone marrow aspirate

Bone marrow trephineBone marrow trephine

Increased destruction of plateletsIncreased destruction of platelets

ImmuneImmune

Idiopathic: Idiopathic:

ITP (acute and chronic)ITP (acute and chronic)

Secondary:Secondary:

Autoimmune disease e.g. SLEAutoimmune disease e.g. SLE

Infections e.g. HIV, Hepatitis CInfections e.g. HIV, Hepatitis C

Drugs e.g. heparin (HIT), quinine, quinidine, Drugs e.g. heparin (HIT), quinine, quinidine, gold gold saltssalts

Lymphoproliferative disease e.g. CLLLymphoproliferative disease e.g. CLL

Neonatal alloimmune thrombocytopeniaNeonatal alloimmune thrombocytopenia

Post-transfusion purpuraPost-transfusion purpura

Increased destruction of plateletsIncreased destruction of platelets

Non-immuneNon-immune

Microangiopathic haemolytic anaemia (MAHA)Microangiopathic haemolytic anaemia (MAHA)

DICDIC

HUSHUS

TTP – idiopathic or 2TTP – idiopathic or 2º e.g. pregnancy, º e.g. pregnancy, infection, infection, metastatic carcinoma, drugs, BMT, AI metastatic carcinoma, drugs, BMT, AI diseasedisease

Pregnancy relatedPregnancy related

Gestational thrombocytopeniaGestational thrombocytopenia

PreeclampsiaPreeclampsia

HELLPHELLP

ManagementManagement

Few spontaneous bleeding problems if plts > 30Few spontaneous bleeding problems if plts > 30

Unless:Unless:

Abnormal platelet functionAbnormal platelet function

Associated coagulopathyAssociated coagulopathy

In general patients need treatment if In general patients need treatment if symptomatic or increased risk of bleeding e.g. symptomatic or increased risk of bleeding e.g. peri/post-operatively, trauma, obstetricperi/post-operatively, trauma, obstetric

In general would want platelets > 50 for minor op In general would want platelets > 50 for minor op and >80/100 for major op. and >80/100 for major op.

May need to transfuse plts if count higher but May need to transfuse plts if count higher but abnormal functionabnormal function

ManagementManagement

May need bone marrow to determine whether May need bone marrow to determine whether cause of thrombocytopenia is failure of cause of thrombocytopenia is failure of production or increased destructionproduction or increased destruction

Stop any possible implicated drugsStop any possible implicated drugs

In general if failure of production:In general if failure of production:

Platelet transfusionsPlatelet transfusions

Treat underlying cause e.g. B12/folate Treat underlying cause e.g. B12/folate replacementreplacement

ManagementManagement

In general if increased destruction:In general if increased destruction:

Avoid platelet transfusions as these are often Avoid platelet transfusions as these are often ineffective and can make clinical situation worse ineffective and can make clinical situation worse e.g. TTP, HITe.g. TTP, HIT

Exception - DICException - DIC

May be required if life-threatening bleeding e.g. ITPMay be required if life-threatening bleeding e.g. ITP

Treat underlying cause e.g. CLLTreat underlying cause e.g. CLL

ITP:ITP:

Immunosuppression – steroids, IVIG, other Immunosuppression – steroids, IVIG, other immunosuppressive agentsimmunosuppressive agents

SplenectomySplenectomy

ManagementManagement

TTP-HUS may require plasma exchange/FFPTTP-HUS may require plasma exchange/FFP

NAIT/PTP may require HPA1NAIT/PTP may require HPA1A A neg pltsneg plts