Hematology Week 1: Primary Hemostasis Flashcards
Categories of Primary hemostatic Disorders
3 listed
- Disorder of platelets
- Disorders of von Willebrand Factor
- Disorders of connective tissue
Primary hemostasis Clinical Presentations
4 listed
Mucocutaneous hemorrhage
- Epistaxis (nosebleeds)
- Menorrhagia or obstetric hemorrhage
- easy bruising, petechiae, purpura
- prolonged bleeding after shaving or body art
Signs and symptoms of both primary and secondary hemostatic disorders
5 listed
- Iron Deficiency Anemia (occult blood loss)
- Bleeding after circumcision or umbilical stump bleeding
- Dental procedure bleeding
- History of transfusion
- Prolonged bleeding after injuries or surgery
Platelet adhesion and shape change
platelets have folds but they bind vWF GPVI activation makes it spread out and cause platelet phospholipid spreading
Alpha granules # per platelet
40-80 per platelet
Alpha granules contain
4 listed
- vWf
- Factors V, VIII, and XIII
- Fibrinogen
- Platelet factor 4 (PF4)
Dense Granules # per platelet
4-8 per platelet
Dense granules contents
3 listed
- stores 60-70% of platelet calcium
- Contains ADP
- Serotonin
Platelet Aggregation Process
3 listed
- Glycoprotein 2b-3a primarily binds fibrinogen
- early platelet activation opens GP 2b/3a to bind fibrinogen
- GP 2b/3a fibrinogen further activates platelets
Platelet Activation: ADP Release and receptors
Dense granules contain ADP and platelets have ADP receptors so it self-stimulates and further activates receptors
Platelet ADP receptor
P2Y Receptor
Platelet Activation: Arachidonic Acid and Thromboxane Signaling
Arachidonic acid is converted into thromboxane A2 (TXA2) by cyclooxygenase 1 (COX-1)
TXA2 can self-stimulate and further activate other platelets
Laboratory tests of platelet function
4 listed
- Bleeding time - time for cessation of bleeding from a standardized wound, not predictive of bleeding in non-symptomatic patients (not really used these days)
- PFA-100 - takes patients whole blood flowing under high shear stress with agonist lined cartridges (collagen-epinephrine or collagen-ADP), platelets aggregate and occlude the aperture (closure time)
- Platelet Aggregation - agonist addition to platelet-rich plasma to trigger platelet aggregation, light transmission increases as platelet aggregation increases
- CBC - for platelet count
Bleeding Time Test
cut patient and time how long it bleeds
time for cessation of bleeding from a standardized wound, not predictive of bleeding in non-symptomatic patients (not really used these days)
PFA-100 Test
takes patients whole blood flowing under high shear stress with agonist lined cartridges (collagen-epinephrine or collagen-ADP), platelets aggregate and occlude the aperture (closure time)
Platelet Aggregation test
agonist addition to platelet-rich plasma to trigger platelet aggregation, light transmission increases as platelet aggregation increases
Glanzmann thrombasthenia is what kind of disorder?
Platelet aggregation disorder
Glanzmann thrombasthenia Clinical Features
Mucocutaneous Hemorrhage
Severe bleeding with trauma/surgery
Glanzmann thrombasthenia Genetics
Congenital
Autosomal Recessive
Glanzmann thrombasthenia Pathophysiology
Loss of GP2b/3a receptor = loss of platelet ability to aggregate to fibrinogen
Glanzmann thrombasthenia Lab Testing
Loss of platelet aggregation to almost all agonists
platelet counts are normal
Glanzmann thrombasthenia Overview
What receptor is missing in Glanzmann Thrombasthenia
GP 2b/3a
Most common Storage Pool Disorders with platelets
Most common is dense granule
Storage pool disorders Etiology
Often autosomal dominant
Clinical Presentations of Storage Pool Disorders
Variable degree of bleeding symptoms
Storage Pool Disorders pathophysiology
Deficiency in dense granules or granule content
Lab testing of storage pool disorders
- Decreased platelet aggregation to ADP agonist
- Normal platelet counts
EM of Platelet Dense Granules
chocolate chip vs sugar cookie
Bernard-Soulier Syndrome Clinical Features
3 listed
- Mucocutaneous Hemorrhage
- Severe bleeding with trauma/surgery
- Thrombocytopenia
Bernard-Soulier Syndrome Etiology
Congenital
Autosomal Recessive
Bernard-Soulier Syndrome Pathophysiology
Defective or absent GP1b Complex
Bernard-Soulier Syndrome Lab Testing
- Low platelet count (<150,000/mm3)
- Normal platelet aggregation to almost all agonists
Bernard-Soulier Syndrome Overview
Bernard-Soulier Syndrome is a disorder of?
Platelet adhesion and thrombocytopenia
What is missing in Bernard-Soulier Syndrome
GP1b complex
thrombocytopenia definition
platelet count of 150,000/mm3
Thrombocytopenia Mechanisms
3 listed
- production failure
- destruction
- sequestration
Acquired Production failure mechanism of thrombocytes
4 listed
- Aplastic anemia
- myelosuppressive therapy (i.e. chemotherapy for leukemia)
- Viral infection (HIV, EBV, CMV, Rubella, and more)
- ethanol abuse
Congenital Production failure mechanism of thrombocytes
Bernard-Soulier Syndrome (congenital thrombocytopenia)
Categories of Platelet destruction mechanisms of thrombocytopenia
2 listed
Immune Mediated
Non-immune mediated
Immune Mediated Platelet destruction mechanisms of thrombocytopenia
3 listed
- Immune thrombocytopenic purpura (ITP)
- Infection (HIV, HepC, Helicobacter pylori)
- Autoimmune disorders (SLE)
Non-Immune Mediated Platelet destruction mechanisms of thrombocytopenia
4 listed
- Disseminated intravascular coagulation (DIC)
- Drug-induced thrombocytopenia (i.e. quinine)
- Sepsis
- Thrombotic microangiopathies (i.e. TTP, Hemolytic uremic syndrome)
Quinine was used for?
To prophylactically treat malaria
ITP AKA
Immune Thrombocytopenic Purpura
ITP Clinical presentations
- isolated thrombocytopenia with no apparent acquired or congenital cause for thrombocytopenia
- Diagnosis of exclusion
ITP Platelet Counts
range from mild to severe thrombocytopenia
ITP Pathophysiology
- Increased platelet destruction by antiplatelet antibodies
- suppressed platelet production
- can also target megakaryocytes preventing platelet production
Acute ITP
- Rapid onset of bleeding symptoms
- Most common form of ITP; typically seen in children < 10 years old
- Spontaneous resolution in <3 months is typical
- Conservative treatment: watchful waiting vs pharmacologic treatment
Chronic ITP
- Typically seen in adults
- can evolve from acute ITP in children
- insidious onset with persistent thrombocytopenia
Acute vs Chronic ITP
ITP Therapies
- Intravenous Immune Globulin (IVIg)
- Glucocorticoids
- Splenectomy
Platelet Sequestration due to splenomegaly mechanism of thrombocytopenia
seen in 2 conditions
- lymphomas
- Cirrhosis (portal hypertension leading to splenomegaly)
Normal sized spleen holds 1/3 circulating platelets
Severe splenomegaly can result in platelet counts < 50,000/mcl
vWF AKA
von Willebrand Factor
vWF binds?
vWF is synthesized by?
Endothelial cells and megakaryocytes
What is vWF?
forms long multimers which binds platelet GP1b
is a carrier protein for factor 8
vWF functions
platelet adhesion to vessel wall
Shear-induced platelet aggregation
Carrier for factor 8
Which vWF multimers have the greatest affinity for GP1b
longer vWF multimers have greater GP1b binding affinity
VWD AKA
Von Willebrand Disease
VWD types
3 listed
type 1
Type 2
Type 3
Type 1 VWD
lower vWF levels
Type 2 VWD
functional vWF abnormality
Type 3 VWD
vWF is virtually absent
What is the most common congenital bleeding disorder?
VWD
1% of the population has VWD
VWD principles of therapy
Dual-defect of hemostasis
Lab test of vWF activity do not always predict the bleeding
VWD Therapy
Desmopressin (DDAVP)
DDAVP AKA
Desmopressin
DDVAVP used to treat?
VWD
DDAVP is?
- a synthetic analog of vasopressin without the vasopressor activity
- most useful type 1 vWD
- I.V. and nasal spray
- Mechanism: triggers release of vWF from Weibel-Palade bodies in endothelial cells
