111 Platelet Disorders Flashcards
What is the treatment of ITP with severe thrombocytopenia without significant bleeding?
Prednisone
Dynamic process in which platelets and blood vessel wall play key roles
Hemostasis
Major regulator of platelet production and where is it synthesized?
Thrombopoietin TPO which is synthesized in the liver
Increased synthesis of platelet is associated with inflammation and what interluekin?
Interluekin 6
What is the average lifespan of platelets?
7 to 10 days
Large multimeric protein present in both plasma and extracellular matrix of the sub endothelial vessel wall which platelet adhere to
VWF
Signals platelet aggregation
Glycoprotein IIb/IIIa
Stabilized platelet plug and develops simultaneously as product of coagulation cascade
Fibrin
Processes that leads to thrombocytopenia
- Decreased bone marrow production
- Sequestration in the spleen
- Increased platelet destruction
Key step in evaluating a patient with thrombocytopenia
Review the peripheral blood smear
What is pseudothrombocytopenia?
In vitro artifact resulting from platelet agglutination via antibodies form the calcium content in the blood collection
(EDTA anticoagulated blood)
Remedy: collect blood in sodium citrate (blue top tube) or heparin (green top tube)
Platelet count to maintain vascular integrity in the microcirculation
Platelet count of 5-10K
Pinpoint non blanching hemorrhages and are usually a sign of decreased platelet number and not platelet dysfunction
Petechaie
Most common noniateogenic cause of thrombocytopenia
Viral and bacterial infection
Platelet count less than 150K. Hgb and WBC count abnormal. Whats the next step?
Bone marrow examination
Platelet count less than 150K. Hgb and WBC count normal. Whats the next step?
Peripheral blood smear
Platelet count less than 150K. Hgb and WBC count normal. PBS show clumped platelets. What’s the next step?
Redraw in sodium citrate or heparin
Platelet count less than 150K. Hgb and WBC count. PBS fragmented RBC. What’s the diagnosis?
Micrioangiopathic hemolytic anemia (DIC, TTP)
Platelet count less than 150K. Hgb and WBC count normal. PBS normal RBC. Normal Platelets. What are the considerations?
Drug induced thrombocytopenia
Infection induced thrombocytopenia
Idiopathic immune thrombocytopenia
Congenital thrombocytopenia
What differentiates HIT from other drug induced thrombocytopenia
- In HIT, thrombocytopenia is not usually severe with nadir counts rarely less than 20K
- Hit is not associated with bleeding but with markedly increased risk for thrombosis
Pathophysiology of HIT
Antibody formation to heparin. Protein platelet factor 4 (PF4) attached to heparin to form a complex. The anti hepatrin/PF4 antibody activates platelets through the FcYRIIa receptor and also activates monocyte and endothelial cells
True or false. HIT is more common in UFH than in LWH.
True
When do patient manifest HIT?
5-10 days after exposure to heparin
4T in the diagnostic algorithm of HIT
Thrombocytopenia
Timing of drop of platelet count
Thrombosis such as localized skin reaction
Other cause if thrombocytopenia not evident
How is HIT diagnosed? What laboratory tests are used for HIT?
HIT remains a clinical diagnosis Test for HIT ELISA with PF4/polyanion complex IgG ELISA Platelet activation assat (serotonin release)
Why is ELISA PF4/polyanion has low specificity in what population of patient?
Low specificity among patibes who undergone cardiopulmonary bypass surgery where 50% develop antibodies postoperatively
Common complication of HIT
Thrombosis both arterial and venous
Drugs effective in HIT thrombosis. How long should it ge given?
Direct thrombin inhibitors like argatroban, bivalirudin
Anti thrombin binding polysaccharides like fondaparinux
Then transitions to warfarin
Given a few days after platelet recovery for for 1 month
Can you give warfarin immediately to HIT thrombosis?
No as aspirin may lead to venous gangrene due to Clotting activation and severely reduced level of protein C and S
Acquired disorder in which there is immune mediated destruction of platelets and possibly inhibition of platelet release from megakaryocyte
Idiopathic thrombocytopenia purpura
Autoimmune disease commonly associated with secondary ITP
SLE
Infections commonly associated with ITP
HIV and hepatitis C
Pathogen assosciated with ITP
H. Pylori
Autoimmune hemolytic anemia with ITP
Evan’s syndrome
Mechanism of action is production of limited hemolysis with antibody coated cells saturating the Fc receptors, inhibiting FC receptor function
Rh0D immune globulin
Rare complication of Rh0D immune Globulin
Severe intrvascular hemolysis
Treatment options for ITP
- Glucocorticoids: prednisone
- Rh0D immune Globulin
- IVIg
- TPO receptor agonist: romiplostim (SQ) and eltrombopag (oral)
Common feature among inherited thrombocytopenia
Large platelets
Group of disorders characterized by thrombocytopenia, micrioangiopathic hemolytic anemia evident by fragmented RBCs. Examples?
Thrombotic thrombocytopenic micrioangiopathies
Examples: TTP, hemolytic uremic syndrome
Differentiate between DIC and thrombocytopenic micrioangiopathies
DIC: consumption of Clotting factors
TTP and HUS: normal PT and aPTT
Other name of inherited TTP
Upshaw-Schulman syndrome
Pathophysiology of TTP
Deficiency of metalloprotease ADAMTS13 which cleaves VWF
Findings to support TTP?
Increased LDH Increased Indirect bilirubin Decreased haptolgobin Increased Reticulocyte count Negative antiglobulin tests
Main stay treatment of TTP
Plasma exchange
Syndrome characterized by acute renal failure, micrioangiopathic hemolytic anemia and thrombocytopenia. Often preceeded by an episode of diarrhea
Hemolytic Uremic Syndrome
Most frequut etiologic serotype of HUs
E coli O157:H7
Primary treatment of HUS
Supportive
Humanized monoclonal antibody against C5 that blocks terminal complement and has efficacy in resolution of HUS
Eculizumab
Causes of thrombocytosis
Iron deficiency Inflammation Cancer Infection Essential thrombocythemia Rarely: 5q- Myelodysplastic process
True or false. Thrombocytosis in response to acute or chronic inflammation is associated with increased thrombotic risk
False.
Inherited disorder absence of platelet Gp Ib-IX-V receptor
Bernard Soulier
Inherited disorder. Absence of platelet Gp IIb/IIIa receptor
Glanzmann thrombasthenia
Classic autosomal dominant qualitative platelet disorder resulting from abnormalities of platelet granule formation
Platelet storage pool disorder
Most common inherited disorders of platelet function prevent normal secretion of granule content
Secretion disorders
Treament for inherited disorders of platelet dysfunction
Platelet transfusion
Tranexamic acid
Desmopressin/DDAVP
Treament for inherited disorders of platelet dysfunction
Platelet transfusion
Tranexamic acid
Desmopressin/DDAVP
Common cause of acquired platelet dysfunction
Medication: antiplatelet or penicillins
What is the platelet dysfunction in Uremia?
Defective adhesion and activation
improved by dialysis or
increasing hematocrit by 27-32%
DDAVP
Most common inherited bleeding disorder
Von willebrand disease
What is the role of VWF
- Major adhesion molecule that tethers the platelet to the exposed subendothelium
- Binding protein for FVIII resulting in significant prolongation of the FVIII half life circulation
Most common type of VWD
Type 1: parallel decrease in VWF protein, VWF function and FVII level
Common manifestation of VWD in female
Menorrhagia
Which blood type has decreased levels of VWF
Blood type O
VWD variant where gene affecting binding of FVIII; also known as autosomal hemophilia
Type 2N
VWD variant describes patient with virtually no VWF and FVIII levels less than 10%
Type 3
VWD variant describes increased susceptibility to cleavage by ADAMTS13
Type 2A
VWD variant describes increased spontaneous binding of VWF to platelets in circulation
Type 2B
Aortic stenosis with GI bleeding; attributed to prescience of angiodysplasia of the GI tract
Heyde Syndrome
Treatment of VWD
DDAVP: releases VWF and FVIII from the endothelial stores
True or false. DDAVP has 2h peak activity when given intranasally compared to 30 mins if IV.
True
Major side effect of DDAVP
Hyponatremia
What the use of vitamin C
Synthesize hydroxy proline which is an essential constituent of collagen
