Coagulation 2 Flashcards
Platelets are produced from?
Cytoplasmic projections of megakaryocytes
Production of platelets is regulated by? What receptor does this interact with?
Thrombopoietin which interacts with the c-MPL receptor
Where is thrombopoietin produced?
The liver and bone marrow stromal cells
How long do platelets circulate for?
7-10 days
What 3 things are secreted by platelets once activated?
- Dense granules
- Alpha granules
- Acid hydrolase
What is the role of TXA2?
Prevents further activation by the agonist
What inherited disorders can cause platelet issues?
Albinism, deafness, and nephritis
What systemic diseases can lead to platelet issues?
Renal, hepatic, and myeloproliferative disease
What are the two types of quantitative disorders?
Thrombocytopenia where the count is reduced
Thrombocytosis where the count is raised
What 3 things can cause thrombocytopenia?
Decreased production, increased destruction, and splenomegaly
What can cause thrombocytosis?
Reactive to infection and autonomous
What is the normal range for platelet count?
150000-400000
What is pseudothrombocytopenia?
When there is clumping of platelets in the presence of EDTA leading to a lower count. Caused by EDTA-dependent antibodies
What 3 things can cause thrombocytopenia?
- Marrow replacement
- Marrow failure as seen in aplastic anemia where fibrosis takes over
- Marrow injury from radiation or drugs
What are the 2 types of inherited thrombocytopenias with small platelets?
Wiskott-Aldrich and X-linked thrombocytopneia
What is the main thrombocytopenia with normal sized platelets?
Familial platelet disorder with predisposition to AML
What are 2 types of thrombocytopenia with large platelets?
Bernard-Soulier and grey platelet syndrome
What is the most common thrombocytopenia due to increased destruction>
Immune thrombocytopenic purpura
What 4 drugs can cause increased platelet destruction?
Heparin, quinidine, vancomycin, and GPIIb antagonists
Post transfusion purpura occurs in those lacking what antigen?
HPA-1a antigen
Most cases of immune thrombocytopenic purpura are?
Acute
Acute ITP is usually preceded by?
Viral infection
Does chronic ITP have something preceding it?
No insidious onset
In isolated thrombocytopenia platelets count will be? What other findings?
Less than 100,000 and they will be large.
Increased megakaryocytes in bone marrow and increased platelet associated IgG
Heparin caused what type of thrombocytopenia? This is most common with what type of heparin?
Immune mediated
Heparin of high molecular weight
The reduced count results in?
Venous and arterial thrombosis, limb loss, death
How do you treat heparin induced thrombocyto?
Discontinue heparin and use a thrombin inhibitor like argatroban or recombinant huridin (refludan)
What are the 3 non-imune associated thrombocytopenias?
- DIC
- Hemolytic uremic syndrome
- Thrombotic thrombocytopenic purpura
What causes TTP?
Reduced ADAMTS-13 metalloprotease activity
How does heparin cause problems?
Binds to PF4 on the platelet leading to an Ig form in against the complex
Hemolytic uremic syndrome occurs in?
Infants and young children
What does hemolytic uremic syndrome cause? What causes it?
Bloody diarrhea
Infection by E. Coli O157:H7
How does hemolytic uremic syndrome differ from TTP?
Less pronounced neurologic symptoms and more pronounced renal symptoms. There is normal ADAMTS13
How is hemolytic uremic syndrome treated?
Dialysis
What are the two types of congenital qualitative disorders?
Disorders of membrane glycoprotein and disorders of intracellular proteins
How is Bernard Soulier syndrome inherited and what does it cause?
Autosomal recessive, leads to abnormal platelet adhesion
There is a defect in what gene in Bernard Soulier?
GP1b gene
How is Bernard Soulier treated?
DDAVP or PLT transfusion
Other than Bernard Soulier what other disorder can cause aggregation problems?
Glanzmann thrombasthenia
How is TTP treated?
Plasmapheresis and steroids
How is hemolytic uremia treated?
Dialysis
Describe the appearance of platelets in Bernard Soulier.
Giant platelets with a pseudonucleus
What are the 4 diseases of dense granule storage pool deficiency?
- Hermansky Pudiak
- Chediak-Higashi
- Thrombocytopenia with absent radii
- Wiskott-Aldrich
Hermansky Pudiak presents with?
Severe oculocutaneous albinism
Chediak Higashi presents with?
Partial albinism, large cytoplasmic granules, defective WBC function
Defects in thromboxane synthesis occur due to?
Defects in the AA pathway
What is an extrinsic acquired qualitative disorder?
Normal platelet but bad environment
What are the 2 causes of extrinsic qualitative
Uremia and paraproteinemia where IgG coats the platelets
What two things can cause intrinsic qualitative disorders?
Drugs and myeloproliferative neoplasms
What is the most frequent inherited bleeding disorder?
von Willebrand disease
How is vWF stored?
Weibel-palade bodies in endothelial cells and alpha granules of platelets
What are the two general functions of vWF?
Adhesion and a carrier protein for factor 8
What can exacerbate bleeding in those with vWF disease?
Aspirin
What types of vWF disease lead to severe bleeding episodes?
2 and 3
How much deficiency is there in vWF type 1? Leads to mild/moderate/severe disease?
Partial deficiency with normal vWF, mild to moderate disease
Type 1 or 3 makes up the majority?
Type 1
Describe vWF disease type 3.
Severe disorder, total or near deficiency of vWF, secondary deficiency of factor 8 and defect in clotting
