ThrombocytopeniaThrombocytopenia

Jason Corbeill PA-CJason Corbeill PA-C

Platelet factsPlatelet facts

Chunks of cytoplasmic fragments of Chunks of cytoplasmic fragments of a megakaryocyte (in bone marrow)a megakaryocyte (in bone marrow)

Surface contains receptorsSurface contains receptors Cytoplasm contains secretory Cytoplasm contains secretory

granulesgranules Lives 8-10 daysLives 8-10 days 1/3 is sequestered in spleen 1/3 is sequestered in spleen

(emergency pool)(emergency pool)

Platelet functionPlatelet function

1. ACTIVATES and releases messenger 1. ACTIVATES and releases messenger molecules/effector enzymesmolecules/effector enzymes

2. ADHERES to area of broken vessel 2. ADHERES to area of broken vessel utilizing Von Willebrand factor.utilizing Von Willebrand factor.

3. Recruits additional platelets 3. Recruits additional platelets (AGGREGATION) with fibrinogen (AGGREGATION) with fibrinogen binding to platelet surface receptors.binding to platelet surface receptors.

4. PROMOTES thrombin production4. PROMOTES thrombin production

The numbersThe numbers

Normal is 150-400kNormal is 150-400k Below 125 or so is concerningBelow 125 or so is concerning Below 50k is very concerning and Below 50k is very concerning and

surgeries should be postponedsurgeries should be postponed Below 10-20k requires PLT Below 10-20k requires PLT

transfusion-risk for spontaneous transfusion-risk for spontaneous bleed.bleed.

Refer to hematologistRefer to hematologist

Signs/Symptoms of low Signs/Symptoms of low plateletsplatelets

Bleeding in areas of weak structural Bleeding in areas of weak structural support (mucous membranes)support (mucous membranes)

Bleeding in areas of dependency Bleeding in areas of dependency (ankles)(ankles)

Signs/Symptoms cont.Signs/Symptoms cont.

Petechiae—small 2-5mm deep red – Petechiae—small 2-5mm deep red – purple flat, non palpable lesions purple flat, non palpable lesions usually in dependent areasusually in dependent areas

Purpura—areas of confluent Purpura—areas of confluent petechiae—can be a few centimeterspetechiae—can be a few centimeters

““blood blisters”—purpura in mouthblood blisters”—purpura in mouth Gingival bleedingGingival bleeding menorrhagiamenorrhagia

Signs/Symptoms contSigns/Symptoms cont

GI bleedingGI bleeding Easy bruisingEasy bruising HematuriaHematuria CNS bleedCNS bleed

3 mechanisms causing a low 3 mechanisms causing a low platelet count :platelet count :

Accelerated destructionAccelerated destruction Impaired productionImpaired production Abnormal distribution Abnormal distribution

(hypersplenism)(hypersplenism)

Differential of Differential of thrombocytopenia due to thrombocytopenia due to accelerated destructionaccelerated destruction

EDTA clumping—lab abnormalityEDTA clumping—lab abnormality ITP-idiopathic (immune) ITP-idiopathic (immune)

thrombocytopenic purpura and it’s thrombocytopenic purpura and it’s mimics.mimics.

HUS-TTPHUS-TTP DIC/sepsisDIC/sepsis Alcohol inducedAlcohol induced HereditaryHereditary HIT (heparin induced thrombocytopenia)HIT (heparin induced thrombocytopenia)

A word about true ITPA word about true ITP

Caused by splenic destruction of PLT due Caused by splenic destruction of PLT due to autoantibody (immune response) that to autoantibody (immune response) that views the platelet as foreignviews the platelet as foreign

Red and white cells are normalRed and white cells are normal Bone marrow is normalBone marrow is normal No splenomegalyNo splenomegaly No lymphadenopathyNo lymphadenopathy Peripheral smear is normal (exc low PLT)Peripheral smear is normal (exc low PLT)

Mimics of ITP via immunologic Mimics of ITP via immunologic pathwaypathway

LupusLupus LymphomaLymphoma CLLCLL Infections (including HIV)Infections (including HIV) SarcoidosisSarcoidosis Solid tumorsSolid tumors MononucleosisMononucleosis Drugs—quinine, quinidine, gold, heparin, Drugs—quinine, quinidine, gold, heparin,

sulfonamidessulfonamides

Treatment for true ITPTreatment for true ITP

Prednisone 1mg/kgPrednisone 1mg/kg IVIGIVIG WinRho if Rh D positiveWinRho if Rh D positive SplenectomySplenectomy VincristineVincristine CyclophosphamideCyclophosphamide RituxanRituxan Romiplostim (Nplate)Romiplostim (Nplate)

A word about HUS-TTPA word about HUS-TTPHemolytic Uremic Syndrome-Hemolytic Uremic Syndrome-

Thrombotic Thrombocytopenic PurpuraThrombotic Thrombocytopenic Purpura

Precipitated by an antibody causing Precipitated by an antibody causing excessive VWF multimers leading to excessive VWF multimers leading to excessive platelet aggregationexcessive platelet aggregation

Small vessel endothelial damage is Small vessel endothelial damage is likely precipitationg factorlikely precipitationg factor

Platelets are used up in forming Platelets are used up in forming microscopic thrombimicroscopic thrombi

Microangiopathic hemolytic anemia Microangiopathic hemolytic anemia as resultas result

Signs/symptoms HUS-TTPSigns/symptoms HUS-TTP

Neurological deficits—confusion, etcNeurological deficits—confusion, etc Renal failureRenal failure ThrombocytopeniaThrombocytopenia Elevated LDHElevated LDH AnemiaAnemia Schistocytes on peripheral smearSchistocytes on peripheral smear Helmet cells/burr cells on peripheral Helmet cells/burr cells on peripheral

smearsmear Purpura/petechiaePurpura/petechiae

HUS-TTP treatmentHUS-TTP treatment

Plasmapheresis--Plasma exchange of Plasmapheresis--Plasma exchange of 40mL/kg daily until PLT > 100k and 40mL/kg daily until PLT > 100k and fall in LDH.fall in LDH.

Supportive careSupportive care No platelet transfusion!!!No platelet transfusion!!!

Special Exam SlideSpecial Exam Slide

HELLP syndromeHELLP syndrome– Hemolysis Elevated Liver enzymes Low Hemolysis Elevated Liver enzymes Low

PlateletsPlatelets– Preeclampsia/eclampsiaPreeclampsia/eclampsia– Recover after deliveryRecover after delivery– May need plasmapheresisMay need plasmapheresis

Many words about DICMany words about DIC(disseminated intravascular (disseminated intravascular

coagulation)coagulation) Under normal circumstances…Under normal circumstances…

– Tissue Factor released at site of injuryTissue Factor released at site of injury– Leads to formation of thrombin at site of Leads to formation of thrombin at site of

tissue injurytissue injury– Leads to activation of platelets and Leads to activation of platelets and

coagulation cascade at site of tissue coagulation cascade at site of tissue injuryinjury

DICDIC

– Leads to local thrombin->fibrinogen-Leads to local thrombin->fibrinogen->fibrin plug>fibrin plug

– Plasmin eventually dissolves plugPlasmin eventually dissolves plug– Whole process is tightly regulated by Whole process is tightly regulated by

inhibitory proteins (antithrombin, Tissue inhibitory proteins (antithrombin, Tissue factor pathway inhibitor)factor pathway inhibitor)

DICDIC

In DIC however..In DIC however..– Tissue factor released at injury siteTissue factor released at injury site– Leads to formation of thrombin at site of Leads to formation of thrombin at site of

tissue injury tissue injury and throughout the entire and throughout the entire vasculaturevasculature

– Leads to activation of Leads to activation of platelets/coagulation cascade platelets/coagulation cascade throughout throughout the entire vasculaturethe entire vasculature

– Leads to platelet, fibrin deposition Leads to platelet, fibrin deposition throughout entire vasculaturethroughout entire vasculature. .

DICDIC

Plasmin, antithrombin, TFPI unable to Plasmin, antithrombin, TFPI unable to keep up with out-of-control coagulation keep up with out-of-control coagulation cascade.cascade.

Results in tissue ischemia, consumption Results in tissue ischemia, consumption of platelets, fibrinogen, coagulation of platelets, fibrinogen, coagulation factors V and VII, prothrombin.factors V and VII, prothrombin.

Leads to bleeding as all components of Leads to bleeding as all components of clotting cascade used up in useless clotting cascade used up in useless clots.clots.

DIC—but wait, there’s more!DIC—but wait, there’s more!

Not only does one have an out-of-Not only does one have an out-of-control activation of the clotting control activation of the clotting cascade in DIC but there is also a cascade in DIC but there is also a second component.second component.

DIC-DIC-FibrinolysisFibrinolysis

Eventually, plasminogen makes Eventually, plasminogen makes plasmin and the widespread fibrin clots plasmin and the widespread fibrin clots begin to break downbegin to break down– Releases fibrin split (degradation) Releases fibrin split (degradation)

productsproducts– FSP enhances bleeding by inhibiting FSP enhances bleeding by inhibiting

platelet aggregationplatelet aggregation– Plasmin also breaks down remaining Plasmin also breaks down remaining

circulating clotting factors and fibrinogen circulating clotting factors and fibrinogen worsening bleeding even more.worsening bleeding even more.

DIC labsDIC labs

So, lab values should show both a So, lab values should show both a consumptive bleeding diathesis AND consumptive bleeding diathesis AND a fibrinolytic process.a fibrinolytic process.– prolonged PT (intrinsic pathway/PTT prolonged PT (intrinsic pathway/PTT

(extrinsic pathway)(extrinsic pathway)– Low fibrinogen (it’s being used to make Low fibrinogen (it’s being used to make

fibrin)fibrin)– Low plateletsLow platelets– Elevated FSP/D-dimerElevated FSP/D-dimer– Low antithrombinLow antithrombin

DIC—why?DIC—why?

Release of tissue factor into Release of tissue factor into circulationcirculation

Extensive vascular endothelial injury Extensive vascular endothelial injury exposing tissue factorexposing tissue factor

Enhanced release of tissue factor by Enhanced release of tissue factor by monocytes in response to various monocytes in response to various cytokines/endotoxins.cytokines/endotoxins.

DIC-Why?DIC-Why?

Infections—bacterial/viral Infections—bacterial/viral – Acute uncompensated DICAcute uncompensated DIC

Malignancy—Trousseau’s syndrome Malignancy—Trousseau’s syndrome (chronic compensated DIC)(chronic compensated DIC)– More thrombotic than bleedingMore thrombotic than bleeding

Aortic aneurysms/hemangiomasAortic aneurysms/hemangiomas Abruptio placentae/retained dead fetusAbruptio placentae/retained dead fetus TraumaTrauma

DIC-Why?DIC-Why?

Snake bitesSnake bites Heat strokeHeat stroke HELLPHELLP

DIC signs/symptomsDIC signs/symptoms

So patients with DIC should show So patients with DIC should show signs/symptoms leading to release of signs/symptoms leading to release of tissue factor and the resultant tissue factor and the resultant widespread thrombus formation and widespread thrombus formation and bleeding diathesis.bleeding diathesis.

DIC signs/symptomsDIC signs/symptoms

Bleeding—from everywhereBleeding—from everywhere Septic shockSeptic shock Renal failureRenal failure Respiratory failure—pulmonary Respiratory failure—pulmonary

hemorrhage/ ARDShemorrhage/ ARDS Hepatic dysfunctionHepatic dysfunction CNS changesCNS changes Evidence of cancer/acute promyelocytic Evidence of cancer/acute promyelocytic

leukemialeukemia

DIC-Treatment DIC-Treatment

Underlying causeUnderlying cause Plasma transfusion ?Plasma transfusion ? Platelet transfusion—only if severe Platelet transfusion—only if severe

bleeding?bleeding? ? Heparin to promote antithrombin-? Heparin to promote antithrombin-

thrombin binding.thrombin binding. ? Antithrombin infusion? Antithrombin infusion

Thrombocytopenia due to Thrombocytopenia due to impaired productionimpaired production

Invasion of marrow by malignant Invasion of marrow by malignant cellscells

Bone marrow hypoplasiaBone marrow hypoplasia– Due to chemo, drugsDue to chemo, drugs

Chloramphenicol, gold, phenytoin, Chloramphenicol, gold, phenytoin, sulfonamidessulfonamides

Thrombocytopenia due to Thrombocytopenia due to impaired productionimpaired production

TreatmentTreatment– Platelet transfusionsPlatelet transfusions– Treat underlying causeTreat underlying cause– Hold offending drugHold offending drug– Amicar—plasmin inhibitorAmicar—plasmin inhibitor

Thrombocytopenia due to Thrombocytopenia due to abnormal distributionabnormal distribution

HypersplenismHypersplenism– Normally 30% of platelets reside in the Normally 30% of platelets reside in the

spleenspleen– In cases of splenomegaly the spleen will In cases of splenomegaly the spleen will

sequester more platelets, resulting in a sequester more platelets, resulting in a decrease in circulating plateletsdecrease in circulating platelets

– Caused by portal Caused by portal hypertension/lymphomahypertension/lymphoma

Thrombocytopenia due to Thrombocytopenia due to abnormal distributionabnormal distribution

Treatment of hypersplenism:Treatment of hypersplenism:– SplenectomySplenectomy– Remember to vaccinate for Remember to vaccinate for

encapsulated organisms prior to encapsulated organisms prior to splenectomysplenectomy

CasesCases

1. So, 35 y/o female truck driver 1. So, 35 y/o female truck driver presents to outpatient clinic with presents to outpatient clinic with bruises.bruises.

CasesCases

2. 55 y/o male in ED s/p MVA with 2. 55 y/o male in ED s/p MVA with multiple open fractures. multiple open fractures. Postoperatively develops PLT 15k, Postoperatively develops PLT 15k, bleeding from everywhere.bleeding from everywhere.

CasesCases

45 y/o female teacher admitted with 45 y/o female teacher admitted with plt count 20.plt count 20.