Bleeding Disorders Flashcards
inherited deficiency of the (1) receptor which normally binds (2) allowing platelet adhesion to the sub-endothelial matrix
- platelet GpIb 2. vWf refers to Bernard‐Soulier syndrome
Qualitative defects in vWF are measured by?
electrophoresis only
Describe type II von Willebrand disease
Qualitative defect due to defective assembly in vWF, resulting in loss of the most active form
Infections‐mechanisms include damage to the vessel integrity by (1)
- bacteria
refers to causes of petechiae or purpura
Where is factor VIII made?
liver
Syndromes which cause collagen defects of the vessel wall
“Scurvy Ehlers-Danlos Cushing’s syndrome”
What is hemophilia B?
X linked recessive disorder of factor IX deficiency
Prothrombin time measures effectiveness of?
extrinsic and common pathways
platelet count, PT, and PTT in hemophilias
platelet count and PT are normal PTT prolonged
What is hemophilia A?
X linked recessive disorder in factor VIII
BINDS PLATELETS AND PROMOTES INTERACTION of vWF AND GLYCOPROTEIN Ib ON PLATELET MEMBRANE; it is the basis for the assay of vWF
RISTOCETIN (antibiotic)
hereditary condition with tortuous dilated blood vessels that easily bleed
hemorrhagic telangiectasia; Weber‐Osler‐Rendu syndrome
Add kaolin and cephalin to plasma and determine clotting time
partial thromboplastin time
PT, PTT, and bleeding time for platelet dysfunction
PT and PTT normal bleeding time prolonged
Treatment of hemophilia A
infusions of recombinant factor VIII
How can bleeding in von Willebrand disease patients be avoided during procedures?
Prophylactic infusions of plasma concentrates containing factor VIII von Willebrand factor
ACTIVATES FACTOR X IN THE INTRINSIC SYSTEM
Factor VIII
Compare and contrast type I and type III von Willebrand disease
both are quantitative defects in amount of vWF type I - Autosomal Dominant; mild to moderate bleeding type III - autosomal recessive; severe bleeding, hemarthrosis (hemophilia like syndrome), very low levels of vWF
DIC is frequently seen in what infections?
sepsis Rocky Mountain Spotted Fever Aspergilosis Malaria Histoplasmosis
Drug induced petechiae or purpura involving skin and mucous membranes pathophysiology
“mechanism usually is immune complex deposition in capillaries and vascular damage”
Causes of bleeding from thrombocytopenia
caused by decreased platelet production, decreased platelet survival (often on an immune basis) or via platelet consumption as in DIC splenomegaly dilution thrombocytopenia
s/s of von Willebrand disease
mild bleeding post-procedure menorrhagia
What organs are typically affected by DIC?
capillaries of brain, adrenal spleen, lungs, liver
ristocetin cofactor activity in von Willebrand disease
decreased
Manifestations of Henoch-Schonlein purpura
“purpuric skin rash, abdominal pain, intestinal bleeding and renal dysfunction”
What is dilution thrombocytopenia?
massive transfusions of blood and blood products (trauma, liver transplant or cardiac surgery) cause a dilution thrombocytopenia which will require platelet transfusion to correct
Add tissue thromboplastin in the presence of calcium ions to plasma and determine clotting time
prothrombin time
The von Willebrand factor binds to (1) in the circulation and allows for increased half‐life of (1). This is essential as unbound (1) has a half‐life of <3 hrs. It also is essential for platelet adhesion to sub endothelial (2) via platelet receptor (3)
- factor VIII 2. collagen 3. GpIb.
DIC is associated with many conditions including?
adenocarcinomas of pancreas, lung, stomach acute promyelocytic leukemia Infections: Sepsis Rocky Mountain Spotted Fever Aspergilosis Malaria Histoplasmosis OB complications trauma burns severe tissue hypoxia acidosis shock snake bite Abdominal aortic aneurysm rupture Heat stroke Acute hemolysis
s/s of hemophilias
bruise easily; major bleeding from trauma or surgery; hemarthrosis leading to fibrotic and deformed joints; petechiae are ABSENT
CAUSES PLATELET ADHESION TO SUBENDOTHELIAL COLLAGEN
vWF
defects in release of platelet (1) which are required for normal platelet function
- ADP and thromboxane refers to storage pool disease
What is the inciting event of DIC?
due to abnormal activation of the coagulation system caused by release of tissue thromboplastin or endothelial damage
DIC is characterized by?
widespread thrombosis leading to microangiopathic hemolytic anemia and organ dysfunction, followed by uncontrolled bleeding
OB complications in which DIC is seen
abruption placentae septic abortion amniotic fluid emboli toxemia of pregnancy
Thrombocytopenia may also be due to conditions causing (1) where there is sequestration of platelets in the enlarged organ
- splenomegaly (cirrhosis e.g.)
Bleeding from conditions that alter blood vessel wall; normal labs:
Causes of petechiae or purpura involving skin and mucous membranes
Amyloidosis Vasculitis Vitamin C deficiency Infections Drug induced (Steroids) Collagen defects Henoch-Schonlein purpura Weber-Osler-Rendu syndrome
Bleeding from conditions that alter the blood vessel walls results in?
petechiae or purpura involving skin and mucous membranes
What are the manifestations of coagulation factor deficiencies?
“bleeding in GI and GU tracts hemarthrosis (bleeding into large joints) prolonged bleeding after procedures”
Partial thromboplastin time measures effectiveness of?
intrinsic and common pathways
What are the complications of DIC?
pulmonary, renal, circulatory failure and severe shock
The effect of aspirin on (1) is irreversible and lasts up to (2) after discontinuing aspirin
- cyclooxygenase 2. one week
inherited deficiency of (1) required to form bridges between platelets and (2) (platelet aggregation).
- Gp IIb‐IIIa 2. fibrinogen refers to Glanzman’s thrombasthenia
Causes of acquired platelet defects
platelet dysfunction from use of plavix or aspirin and other non‐steroidal anti‐inflammatory drugs uremia
Bleeding from conditions that alter blood vessel wall; normal labs:
Lab findings in petechiae or purpura involving skin and mucous membranes
normal platelet count, PT and PTT and bleeding time
Treatment of hemophilia B
Recombinant factor IX concentrates
How do factor VIII levels predict severity of bleeding in hemophilia A? What are the cutoffs?
Factor VIII levels 1% of normal –> severe bleeding Factor VIII levels 2-5% of normal —> mild bleeding
septicemia secondary to meningococcal or rickettsia infection
infectious cause of petechiae or purpura involving skin and mucous membranes
What is the purpose of vWf binding to factor VIII?
increases half-life essential for platelet adhesion
Heterozygote females can also rarely acquire the disorder from inactivation of the remaining normal Xchromosome
Hemophilia A
What are the coagulation factor deficiencies? Which are inherited and which are acquired?
Inherited: Factor VIII Factor IX von Willebrand disease Acquired: DIC
Where is vWF made?
endothelial cells
What are the s/s of platelet dysfunction?
“Petechiae Easy bruising Nosebleeds Menorrhagia”
What are some of the acquired coagulation disorders?
vitamin K deficiency parenchymal liver disease (cirrhosis)
Platelets, factor VIII, PTT in von Willebrand disease
platelet counts normal factor VIII decreased PTT prolonged in types I and III
