Transcript View

Thrombocytopenia
Sheryl L. Ziegler, D.O.
2017
Hemostasis
Subendothelial matrix
WBC
Hemostatic plug
Platelets
Fibrin
Endothelial cell
RBC
WBC
Platelets
 Normal Hemostasis requires adequate #
functioning platelets
 Increased chances of bleeding as platelet
count falls
 Normal individual -- 10,000 platelets
 Surgery -- often >50,000 needed
Thrombocytopenia & Bleeding
Testing platelet disorders – function and count
Bleeding Time Test
Thrombocytopenia
Clinical Features
 No specific or unique features
 MUCOCUTANEOUS BLEEDING
 Bleeding form multiple sites
 Mucous membranes, nose
 GI tract
 Skin
 Vessel puncture sites
 Petechial rash of skin or mucous membranes
Normal Platelet Kinetics
 # =150,000 - 400,000
 Life span 9-10 days
 35,000 new platelets produced each day
 Megakaryocyte
Thrombocytopenia
Clinical Features - Lab
 Most often diagnosis is made by lab
 Platelet agglutination may give falsely low
value secondary to:

Clotting/platelet agglutination
 Pseudothrombocytopenia

Examine the smear
Causes
Thrombocytopenia
Several Disease Mechanisms
Thrombocytopenia
Decreased Production
Increased Destruction
Increased pooling in spleen
Thrombocytopenia
Several Disease Mechanisms
Thrombocytopenia
Decreased Production
Increased Destruction
Increased pooling in spleen
Decreased production
 Marrow damage
 Aplasia
 Drugs/Toxins
 Malignancy
 Hepatitis
 Ineffective production
 Decreased vitamin
B12
 Decreased folate
 Congential
 Fanconi’s anemia
 TAR syndrome
Aplastic Anemia
Marrow Damage
 Decrease in all cell lines
 2 per million
 More common in children
 Due Bone Marrow Bx for DX – “Empty Marrow”
Symptoms – Aplastic anemia
 Related to anemia

Fatigue, Shortness of breath
 Related to low white cell count

Infections
 Related to thrombocytopenia

Bleeding (mucous membranes)
 High mortality of “untreated” severe Aplastic
anemia

80% at 1 year
Causes
Idiopathic
Unknown
Drugs
Benzene
Hepatitis
Pregnancy
Treatment
 Bone marrow transplantation – Younger
 Immunosuppression – Older
 Antithymocyte globulin (ATG) + Cyclosporine

70% response rate
long term survivals 65-90%

no difference in long-term survival

Drugs/Toxins
Marrow Damage
 Alcohol
 Reversible
Infiltrative processes
Marrow Damage
 Malignancies





Multiple myeloma
Acute leukemia
Lymphoma
Myelofibrosis
Metastatic carcinoma
Often all cell lines are affected. Can see tear drop cells.
Ineffective production
 Decreased Vitamin B12
 Decreased folic acid
 Check levels

Takes about 3 months to deplete folate
Takes about 2-3 years to deplete B12

Patients with also have macrocytic anemia

B-12/Folate Deficiency
Ineffective Production
 Alcoholics
 “Tea and Toast” elderly patients
 Homeless
 Pernicious anemia
 Gastric surgery (poor absorption)
 Platelet production is rapidly reversed with
appropriate vitamin Rx
Defective Production - Therapy
 Reverse production abnormality



Treat the underlying cause
Leukemia -- effective Rx
B-12 or Folate Deficiency
 Irreversible marrow damage

chronic transfusions may be needed
Platelet Transfusions
 Random donor platelets
 Most common order

Each 6 pack should raise the platelet count by 50,000

Contain very few RBCs & do not need to be ABO
compatible
Infectious risks
Fevers, chills, hypotension reactions


Thrombocytopenia
Several Disease Mechanisms
Thrombocytopenia
Decreased Production
Increased Destruction
Increased pooling in spleen
Pooling in Spleen
 Spleen Functions like a large sponge



Liver Disease
Myeloproliferative
Myelofibrosis
Disorders of Distribution
 Normally 1/3 of platelets stored in spleen
 Increased spleen = increased trapping
 Splenomegaly should not cause < 50,000


if lower --- concomitant defect
Most common – advanced liver disease
Myelofibrosis
Disorders of Distribution
 Myeloproliferative disorder
 Marrow replaced by connective tissue
 Extramedullary hematopoiesis occurs in
the spleen
Thrombocytopenia
Several Disease Mechanisms
Thrombocytopenia
Decreased Production
Increased Destruction
Increased pooling in spleen
Increased destruction
 Nonimmune
 DIC
 TTP/HUS
 HELLP
 Immune
 Drugs
 ITP
 Autoimmune
Disseminated Intravascular
Coagulation (DIC)
Non-immune Destruction Disorders
 SICK PATIENTS – Septic, shock, placental
abruption, major trauma, etc.
 Entire coagulation pathway is activated
 Both pro-coagulant and anti-coagulant
DIC
 Severe thrombocytopenia
 Patients can bleed and clot
 Marked prolongation of the coagulation
factors (PTT/PT)
 Elevated D-Dimer
 Microangiopathic anemia
 Treat underlying cause
Thrombotic Thrombocytopenic
Purpura (TTP)
 Five Clinical Features





Thrombocytopenia
Red Cell Fragments
Fever
Renal Failure
Neurologic Features
TTP
 High mortality > 90% without treatment
 Usually affects young women
 Platelet thrombus formation

No increased PT/PTT
 Arterial platelet thrombi “white clots”
VWF, ADAMTS13 and Platelet Adhesion
With ADAMTS13
Without ADAMTS13
Normal VWF Multimers
Normal Hemostasis
Ultralarge VWF Multimers
Microvascular Thrombosis
(TTP)
VWF Cleaving Protease (ADAMTS13)
Idiopathic TTP – Initial Therapy
Initiate treatment:
• Plasma exchange
• Prednisone
Avoid:
• Platelet transfusions
Thrombocytopenia
Autoimmune
 Drug induced
 Infectious diseases
 Idiopathic (ITP)
Autoimmune Thrombocytopenia
Clinical
 Platelet count can be as low a 1,000
 Increased # of megakaryocytes

Compensates for shortened platelet survival

Increased MPV (larger immature platelets)
Heparin-Induced Thrombocytopenia
 Non-immune related



Very common
Mild decrease in platelet number
Usually clinical insignificant
 Immune related


Must diagnosis !!!
Marked decrease in platelets


Less than 50K
Greater than 50% decline from baseline
Incidence of HIT
 HIT occurs in up to 5% of patients
receiving unfractionated heparin (UFH)
 Up to 1% incidence with low molecular
weight heparin (LMWH)
 Immune-mediated allergic reaction to
heparin/platelet factor 4 complex
Gruel et al. Br J Haematol. 2003;121;786-792; Warkentin. J Crit Illness. 2005:20(1):6-13.
Temporal Patterns of
Thrombocytopenia in HIT
Heparin (re) Exposure
Rapid-onset
HIT
(hours-days)
Day 1
Day 5
Typical-Onset HIT
Mean day 9
(5-14 days)
DelayedOnset HIT
(9-40+ days)
Day 14
THROMBOCYTOPENIA (± THROMBOSIS)
Day 30
Clinical events associated with HIT
 Venous thrombosis (30-70%)
Deep vein thrombosis (DVT)
 Pulmonary embolism (PE)
 Adrenal necrosis (adrenal vein thrombosis)
 Cerebral venous (sinus) thrombosis
 Venous limb gangrene (VKA associated)
Arterial thrombosis (“white clots”) (15-30%)
 Limb artery thrombosis
 Stroke
 Myocardial infarction
Skin lesions at heparin injection sites (10%)
 Skin necrosis
 Erythematous plaques
Acute reactions after i.v. heparin bolus (10%)
Disseminated intravascular coagulation (DIC) (10%)





MORTALITY = 20-30%
Heparin-induced
Thrombocytopenia (HIT)
Immune Destruction
 Stop all heparin
 Order Heparin Induced Antibody
 Tx – Direct thrombin inhibitors


Lepirudin
Argatroban
Idiopathic Thrombocytopenia Purpura
(ITP)
 Unrelated to:



Drug
Infection
Autoimmune Disease
 Diagnosis

Made by excluding all other causes of
nonimmune & immune destruction
Idiopathic Thrombocytopenic Purpura
Laboratory
 Platelets demonstrate better than normal
function
 Count = 1,000 to 100,000
 Normal to increase # of Megakaryocytes

Increased ploidy in the marrow
Idiopathic Thrombocytopenic Purpura
Presentation
 Abnormal Bleeding





Petechial & purpuric lesions of skin & mucous
membranes are most typical
Bruising
Recurrent epistaxis
Menorrhagia
Thrombocytopenia must become severe
before bleeding becomes a problem
Recommended platelet counts to
avoid bleeding
Idiopathic Thrombocytopenic
Purpura
 Infusion of plasma from
ITP patients into normal
patients causes
thromboctyopenia
Laboratory Tests
 Platelet Antibodies



Determines the presence of IgG, IgM &/or
complement on platelet surface
Strong Ab test suggests an autoimmune
destruction like ITP
Not very good sensitivity or specificity

Can be positive with
 Liver disease
 Sepsis
 Malignancies
Idiopathic Thrombocytopenic
Purpura
Therapy & Clinical Course
 Platelet transfusions

Most patients destroy most of the product
 Platelet transfusion if life threatening
hemorrhage or intracranial hemorrhage
ITP – Therapy
 No treatment – if platelets > 30K
 Steroids
 IVIgG
 WinRho
 Rituximab
 Splenectomy
 Promacta –
 Nplate -
most effective
most effective
THE END