BL- Platelet disorders Flashcards
4 events in the formation of a platelet plug
Platelet adhesion
Platelet activation
Platelet aggregation
Fibrin formation and support of local coagulation
Platelet Precursor
Megakaryocyte in bone marrow
How long do platelets circulate
Bud off, circulate 7-10 days
TPO: thrombopoietin
main growth and maturation factor for megakaryocytes
Platelet adhesion
Platelet activation
Platelet aggregation
Fibrin formation and support of local coagulation
4 events in the formation of a platelet plug
- inhibits coagulation
- prevents platelet aggregation
- promotes clot breakdown
- provides barrier to reactive elements in the vessel wall
Normal Endothelium:
main growth and maturation factor for megakaryocytes
TPO: thrombopoietin
Glycoproteins on _____ are receptors for adhesive proteins present in the vessel wall and in plasma
platelet surface
Who attracts platelets well?
Von Willebrand factor
*Temporary bond between GPIb (platelet) and vWF
Granules of Plts
Dense Granules
Lysosomes
Alpha granles
_______granules release serotonin ( vasoconstriction) , ADP platelet activation, calcium (further activation, adhesions and aggregation) of other platelets
Dense
_________stick to activated platelets and are themselves activated through release of compounds that further amplify platelet activation
New platelets
Platelets adhere to damaged vessel wall directly via collagen or indirectly via von Willebrand factor
Plt Adhesion
Excitatory agonists (collagen, thromboxane A2, etc.) cause a conformational change in platelet to expose Glycoprotein IIbIIIa binding sites for fibrinogen
Plt activation
Platelets are laced together through fibrinogen bridges
plt Aggregation
Locally, thrombin converts the fibrinogen to fibrin stabilizing
Fibrin formation
Thrombocytopenia
(decreased numbers of platelets)
Normal platelet count between
150,000-400,000/ul
may see spontaneous hemorrhage and increased risk of hemorrhage with trauma or surgery
Platelets 20–50,000
*Platelets <10,000-20,000: can see life-threatening spontaneous hemorrhage
- Decreased production of platelets
- Increased destruction of platelets
- Distribution disorders (Increased sequestration of platelets due to splenomegaly)
- Dilution (massive transfusion)
Causes of Thrombocytopenia
Low platelets in the setting of pancytopenia
~In the elderly think of Myelodysplastic syndrome (high MCV) and other hem malignancies (non-Hodgkin’s Lymphoma)
~Nutritional deficiencies (B12/Folate)
Very common cause of low platelets
Can be seen in bacterial and viral infections
Viral: HIV, hepatitis C
Infection- common cause of low platelets
Disease of children or young adults following viral infection
Sudden onset severe thrombocytopenia with petechiae and nosebleeds
Recovery in 2-6 weeks without treatment or after steroids
Acute ITP
Adults
Often have concurrent autoimmune disorders (e.g. SLE, RA), lymphoma, or HIV, though most cases idiopathic
Primary ITP is therefore a diagnosis of exclusion
Treatment options include steroids, IVIG, splenectomy, TPO receptor agonists
Chronic ITP ( by definition >12 months):
a disorder that can lead to easy or excessive bruising and bleeding. The bleeding results from unusually low levels of platelets — the cells that help your blood clot.
Idiopathic thrombocytopenic purpura (ITP)
Most common congenital bleeding disorder Usually autosomal dominant Abnormality in platelet/endothelial interaction Clinical problems: Mucosal bleeding Nose bleeds GI bleeds Menorrhagia Bleeding after surgery if no correction
Von Willebrand Disease
Adhere platelets to exposed collagen that acts as scaffolding for vWF at the site of a wound or vessel disruption
Von Willebrand protein fx
Carry Factor VIII
Without this protein, Factor VIII has a VERY short half-life
Von Willebrand protein fx
Platelet Function Analyzer (PFA) (measures 1st function of the vW protein)
Tests for von Willebrand’s Disease:
Screening test
Type 1: Partial quantitative vWF deficiency. 70-80% cases
Type 2: Qualitative defects – either decreased (2A) or increased (2B) adhesion to platelets with latter accelerating vWF clearance. 15-30% cases
Type 3: Almost complete absence vWF. Rare
Types of von Willebrand’s Disease
Factor VIII level normal or decreased (measures 2nd function of vW protein)
Tests for von Willebrand’s Disease:
Qualitative defects – either decreased (2A) or increased (2B) adhesion to platelets with latter accelerating vWF clearance. 15-30% cases
Type 2- Types of von Willebrand’s Disease
measures amount of vW protein
Tests for von Willebrand’s Disease:
Partial quantitative vWF deficiency. 70-80% cases
Type 1- von Willebrand’s Disease
Almost complete absence vWF. Rare
Type 3- von Willebrand’s Disease
Von Willebrand Disease Treatment - DDAVP
DDAVP (arginine vasopressin) enhances already synthesized vWF release from endothelial stores so effective in type 1 but not type 2 or type 3 disease
Other platelet function disorders
- Congenital
- Drug induced ( aspirin, NSAIDs, Plavix)
- Uremia
- Liver disease
- Myeloproliferative disorders
__________ from obvious trauma suggests local vascular defect
Brisk bleeding
____________ is more likely a generalized hemostatic disorder
Prolonged or recurrent bleeding
___________ from injured site raises the possibly of excessive fibrinolysis or abnormal crosslinking of fibrin
Sudden resumption of bleeding
_________ suggests a more severe, generalized hemostatic disorder
Multiple site bleeding
Disorders can be classified as either qualitative (abnormal function) or quantitative (not enough or too
many platelets). They can be further classified as congenital or ________.
acquired
Qualitative Platelet Disorders
Von Willebrand disease (vWD) Bernard-Soulier syndrome gray platelet syndrome afibrogenemia Glanzmann thrombasthenia
Quantitative Platelet Disorders
immune thrombocytopenic purpura (ITP)
Alloimmune thrombocytopenia
DIC, sepsis, thrombotic thrombocytopenic
purpura (TTP), and hemolytic uremic syndrome (HUS)
Disorders can be classified as either qualitative (abnormal function) or _____(not enough or too
many platelets). They can be further classified as congenital or acquired.
quantitative
the most common congenital bleeding disorder.
Von Willebrand disease (vWD)
a rare autosomal recessive disorder where expression of GP1b on the platelet surface is reduced, leading to a defect in platelet adhesion. Platelet aggregation studies only show abnormal aggregation with ristocetin.
Bernard-Soulier syndrome
Storage pool deficiencies can occur, with a deficiency of either dense granules or α-granules. Deficiency of α-granules is known as
gray platelet syndrome
leads to both primary (platelet plug formation) and
secondary (formation of cross-linked fibrin) hemostatic defects.
afibrogenemia
rare autosomal recessive bleeding disorder caused by absent or defective GPIIb-IIIa
Glanzmann thrombasthenia
Thrombocytopenia (a low platelet count) can be due to decreased platelet production, increased platelet destruction or consumption, or _______ of platelets in the spleen.
sequestration
The most common cause of thrombocytopenia due to increased destruction is:
immune thrombocytopenic purpura (ITP)
occurs when a patient develops antibodies to platelet antigens not present on the patient’s own platelets
Alloimmune thrombocytopenia
Other nonimmune-mediated
causes of thrombocytopenia include:
DIC, sepsis, thrombotic thrombocytopenic
purpura (TTP), and hemolytic uremic syndrome (HUS).
Platelet count and blood smear to evaluate for thrombocytopenia or other hematologic
abnormalities
Basic screening tests when evaluating excessive bleeding
Mild cases of ______disease may require repeated testing to establish a diagnosis if clinical suspicion remains.
von Willebrand
Thrombin clotting time (TCT) to evaluate for fibrinogen defects, the presence of fibrin split products, or heparin effects
Fibrinogen level
Basic screening tests when evaluating excessive bleeding
Bleeding time or platelet function analyzer (PFA-100) to evaluate primary hemostasis
Basic screening tests when evaluating excessive bleeding
APTT as a screening test for the intrinsic coagulation pathway
PT/INR as a screening test for the extrinsic coagulation pathway
Basic screening tests when evaluating excessive bleeding
