Bleeding DIsorders Flashcards
The platelet count will show (qualitative / quatitative) disorder of platelets? What is the normal value?
quantitative; 150,000 - 300,000 platelets/microliter (isnt it supposed to be 450,000???)
If the platelet count is normal, bleeding time will show (qualitative / quatitative) disorder of platelets?
qualitative
Abnormal clotting time shows an abnormality in?
Extrinsic, Intrinsic and Common coagulation factors
Prothrombin time (PT) assesses (intrinsic / extrinsic) pathway in addition to the common pathway? Enumerate factors involved.
Extrinsic factors; F V, VII, X, prothrombin, fibrinogen
Activated Partial Thromboplastin time (aPTT) assesses (intrinsic / extrinsic) pathway in addition to the common pathway? Enumerate factors involved.
Intrinsic; F V, VIII, IX, X, XI, XII, prothrombin, fibrinogen
Excessive bleeding can result from?
Increased fragility of vessels, platelet deficiency, derangement of coagulation
In bleeding diorders with vessel wall abnormality, platelet count, bleeding time, PT, PTT are all (increased/decreased/normal)
NORMAL
What are the common causes of vessel wall abnormality
Infections, drug reactions, scurvy, Ehler’s Danlos, Henoch-Schonlein purpura, Hereditary hemorrhagic telangectasia (Weber-Osler-Rendu Syndrome), Perivascular amyloidosis
Describe the vessels in hereditary hemorrhagic telangectasia (Weber-Osler-Rendu Syndrome). Most common sites of bleeding?
Dilated and tortuous with thin walls; mucous membranes of nose, tongue, mouth, eyes, GIT
What causes Henoch-Schonlein purpura?
deposition of circulating immune complexes within the vessels and glomerular mesangial regions
At what platelet level is considered thrombocytopenia?
less than 100,000 platelets/microliter
At what platelet level does spontaneous bleeding become evident?
less than 20,000 platelets/microliter
What is the most feared (hahaha wtf??) complication of thrombocytopenia?
intracranial bleed
Platelet levels of 20,000 - 50,000 can aggravate ________ bleeding
post traumatic
(T/F) You should transfuse a patient (not undergoing surgery) when platelets are <20,000
False, do not transfuse unless symptomatic b/c body might produce antibodies against transfused platelets
Bleeding from thrombocytopenia is associated with (increased/decreased/normal) PT & PTT and often involves small vessels
Normal
Causes of thrombocytopenia
Decreased platelet production Decreased platelet survival Sequestration Massive transfusion / dilution Ineffective megakaryopoesis
Heparin causes a _______in platelet count
decrease
An autoimmune disease producing antibodies against platelets wherein there is a normal bone marrow (or increased megakaryocytes)
Idiopathic Thrombocytopenic Purpura (ITP)
Differences in population affected between acute and chronic ITP
Acute is self-limited an seen in childrenof any gender 1-2 weeks after a viral infection; Chronic is seen in adults especially in pregnant wormen with autoimmune disorders
In Chronic ITP, autaoantibodies are directed against platelet membrane glycoprotein of this type
Gp IIb/IIIa or Ib-IX
What Ig class is usually seen in chronic ITP
IgG
In chronic ITP, what is the alternative treatment to steroids? How does it help?
splenectomy. Removal of the source of autoantibodies
(T/F) Platelet concentrate transfusion in patients with ITP is helpful
False. Antibodies will just destroy the platelets
What is the characteristic pentad of thrombotic thrombocytopenic purpura (TTP)
1) Microangiopathic hemolytic anemia
2) Decreased platelets
3) Fever
4) Transient neurologic defects
5) Renal failure (usually in females, 4th decade of life)
Morphology in TTP
Widespread hyaline microthrombi
What is the enzyme deficiency in TTP?
ADAMTS 13 or vWF metalloprotease
What is the function of the enzyme ADAMTS 13?
degrades vWF
What are the main functions of vWF?
Platelet adhesion
Carry factor VIII and improve its lifespan
What is the treatment for TTP
Plasma exchange
What would be a differential diagnosis for TTP? How do you differentiate?
Hemolytic Uremic Syndrome (HUS). HUS does not have associated neurologic manifestations & ADAMTS 13 levels are normal
What is the etiology of HUS?
Bacterial toxin (EHEC) that stimulate platelet aggregation
What is the cause of typical HUS?
O157:H7 elaborates shiga-like toxin that alters endothelial cell function when absorbed, causing platelet activation and aggregration
What is the cause of atypical HUS?
Defect in complement factor H, CD46 or factor I
Examples of inborn/congenital abnormalities in platelet function
Von WIlldebrand Disease, Bernard soulier Syndrome, Glanzmann Thrombasthenia, Disorders of platelet secretion
Reasons for acquired abnormalities in platelet function
Aspirin or NSAIDS, Uremia
What is the most common inherited bleeding disorder in humans?
Von Willdebrand disease
aPTT & PTT is _____ in Von Willdebrand disease and platelet count is _______; Risotcetin aggregation test is _______
elevated; normal; reduced
What is defective in Von Willdebrand disease
vWF causing defective adhesion
Which types of Von Willdebrand disease are associated with reduced quantity of circulating vWF? Which one autosomal recessive and is associated with extremely low levels of vWF?
Type 1 and 3; Type 3
Type 2 Von Willdebrand disease is characterized by ________ defect in vWF
Qualitative
Type 1 Von Willdebrand disease is autosomal _______?
dominant
In type 2 Von Willdebrand disease, ______ mutations cause defective multimer assembly
missense
In Bernard Soulier Syndrome, defective adhesion is caused by the lack of ______?
GpIb
Lack of GpIIb/IIIa in Glanzmann Thrombasthenia causes defective _______?
aggregation
In acquired platelet abnormalities d/t uremia, the platelet count is ______ and the BT is ______
Normal; Elevated
The complex pathogenesis In acquired platelet abnormalities d/t uremia involves defects in ____, _____ and ______.
aggregation, adhesion and granule secretion
Increased clotting time with normal platelet and BT is indicative of abnormalities in ____?
Clotting factors
Abnormalities in extrinsic pathway factors will show an elevated ______?
PT
Abnormalities in intrinsic pathway factors will show an elevated ______?
PTT
vWF is synthesized in by?
endothelial cells and megakaryocytes
What is the most important function of vWF?
Promote adhesion of platelets to the subendothelial matrix
vWF stabilizes factor ____
VIII
factor VIII is an essential cofactor of factor
IX
What is the most common hereditary disease that is associated with life-threatening bleeding?
Hemophilia A
Hemophilia A is caused by a deficiency in factor ____
VIII
Hemophilia B (aka Christmas disease) is caused by a deficiency in factor ____
IX
Hemophilia ___ is associated with normal PT and prolonged PTT
A and B
(T/F) Both hemophilia A & B are recessive x-linked traits
True
What is required for the diagnosis of hemophilia?
Specific assays of factor levels
Liver disease and Vitamin K deficiency affects the following factors
II, VII, IX, X
Disseminated Intravascular Coagulation (DIC) is caused by
excessive activation of coagulation leading to the consumption of platelets, fibrin and coagulation factors
DIC is not a primary disease, it is caused by complications of conditions such as:
Obstetric complications / difficult labor
Neoplasms
Infections/sepsis
Massive tissue injury
Give some triggers of DIC
Release of tissue factor or thromboplastic substances into circulation and widespread injury to endothelial cells
Widespread injury to endothelial cells can be seen in
Bacterial infections
Massive trauma
Obstetric conditions
Neoplasms
Possible consequences of DIC
WIdespread deposition of fibrin and microangiopathic hemolytic anemia
Hemorrhagic diathesis
In DIC, thrombi are usually seen in the
Kidneys, alveolar capillaries, CNS, adrenals, spleen, liver
Waterhouse Friedrichsen Syndrome is d/t
massive adrenal hemorrages
Widespread microthrombi in the placenta causing premature atrophy of the cytotrophoblasts and syncytiotrophoblast
Sheenhan postpartum pituitary necrosis
What is the definitive treatment for DIC?
Removal or treatment of inciting cause
DIC is characterized by
microangiopathic hemolytic anemia Dyspnea, cyanosis, renal failure Convulsions, coma Oliguria, acute renal failure Sudden or progressive circulatory failure / shock
