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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