Ch 4 Pathoma - Hemostasis and Related Disorders Flashcards
______ of the blood vessel is needed to carry blood to tissues. Damage to the wall is repaired by _____, which involves formation of a _____ at the site of vessel injury. It occurs in two stages (primary and secondary)
Integrity; hemostasis; thrombus (clot)
Primary hemostasis forms a ____ ___-____ and is mediated by interaction between ___ and the _____.
weak platelet-plug; platelets; vessel wall
Secondary hemostasis ____ the platelet plug and is mediated by the ____.
stabilizes; coagulation cascade
Which stage of hemostasis forms a weak platelet plug?
primary hemostasis
Which stage of hemostasis is mediated by the coagulation cascade?
secondary hemostasis
Name the four steps of primary hemostasis.
1) Transient vasoconstriction of the damaged vessel; 2) Platelet adhesion to the surface of the disrupted vessel; 3) Platelet degranulation; 4) Platelet aggregation
Step one of primary hemostasis, ______, is mediated by _____ and ____ release from endothelial cells.
transient vasoconstriction; reflex neural stimulation; endothelin
In step 2 of primary hemostasis, _______, ____ binds exposed ____. Then platelets bind ____ using the ___ receptor.
platelet adhesion; Von Willebrand factor (vWF); subendothelial collagen; vWF; GPIb
Von Willebrand factor is derived from _____ of endothelial cells and _____ of platelets.
Weibel-Palade bodies; alpha-granules
Adhesion of platelets induces ____ and ____ with release of multiple mediators including ___ and ___.
shape change; degranulation; ADP; TXA2
step 3: platelet degranulation
In step 3 of primary hemostasis, _____, ADP is released from platelet _____. It promotes the exposure of _____ receptor on platelets (needed for ____). Also, TXA2 is synthesized by platelet ____ and released. It also promotes ____.
platelet degranulation; dense granules; GPIIb/IIIa; platelet aggregation; COX; platelet aggregation
Platelets aggregate at the site of injury via ____ using ___ (from plasma) as a linking molecule. This results in the formation of a ______. ____ helps stabilize it.
GPIIb/IIIa (ADP promotes exposure of the receptor); fibrinogen; weak platelet plug; coagulation cascade (secondary hemostasis)
(step 4: platelet aggregation)
Disorders of primary hemostasis are usually due to abnormalities of _____. They can be divided into ____ or ____. Clinical features include ___ and ___ bleeding.
platelets; quantitative or qualitative; mucosal; skin
Name the 6 symptoms of mucosal bleeding (and name the most common and most sever)
epistaxis (most common); hemoptysis; GI bleeding; hematuria; menorrhagia; intracranial bleeding (severe)
Name the 4 symptoms of skin bleeding (and which one is a sign of thrombocytopenia and not usually qualitative disorders)
petechiae (1-2mm; quant, not qual); purpura (greater than 3mm); ecchymoses (greater than 1cm); easy bruising
A normal platelet count is ____. Less than ___ leads to symptoms. A normal bleeding time is ____. Prolonged with qualitative or quantitative platelet disorders? Blood smear is used to assess ___ and ___ of platelets. BM bx used to assess ____.
150-400 K/microL; 50; 2-7 minutes; both!; number and size; megakaryocytes (produce platelets)
_____ is an autoimmune production of ____ against platelet antigens (e.g. ____). It is the most common cause of thrombocytopenia in both ____ and ___.
Immune thrombocytopenic purpura (ITP); IgG; GPIIb/IIIa; children; adults
In ITP (immune thrombocytopenic purpura), autoantibodies are produced by ____ in the ____. Antibody-bound platelets are consumed by ____ resulting in ____.
plasma cells; spleen; splenic macrophages; thrombocytopenia
Acute ITP arises in ____ weeks after a ___ or ____. It is self-limited, usually resolving within days/weeks/months of presentation.
children; viral infxn; immunization; weeks
immune thrombocytopenic purpura
Chronic ITP arises in ____, usually ____. May be ____ (unknown cause) or ____ (e.g. SLE). May cause short-lived thrombocytopenia in offspring because _____.
adults; WOCBP; primary; secondary; anti platelet IgG can cross the placenta
(immune thrombocytopenic purpura)
Lab findings in ITP include high/normal/low platelet count (often ___); high/normal/low PT/PTT; high/low/normal megakaryocytic on bx.
low; less than 50; normal (coag factors not affected since this is a primary hemostasis disorder); high (bone marrow is trying to compensate for low platelets)
Initial treatment for ITP is ____. ____ respond well; ____ may show early response but often relapse. ____ is used to raise the platelet count in symptomatic bleeding, but its effect is long/short. ____ eliminates the primary source of antibody and the site of platelet destruction (performed in ___ cases)
corticosteroids; children; adults; IVIg; short; splenectomy; refractory
_____ is the pathologic formation of platelet microthrombi in small vessels. Platelets are ___ in the formation of microthrombi, and RBCs are ___ as they cross the microthrombi, resulting in ____ with ___.
Microangiopathic hemolytic anemia; consumed; sheared; hemolytic anemia; schisotcytes
Microangiopathic hemolytic anemia is seen in these 2 disorders. Tx involves ___ and ____, particularly in ____.
Thrombotic thrombocytopenia purpura (TTP) and hemolytic uremic syndrome (HUS); plasmapheresis (remove autoantibody); corticosteroids (decrease production of autoantibody); TTP
Thrombotic thrombocytopenic purpura (TTP) is due to decreased _____, an enzyme that normally cleaves ___ multimers into smaller monomers for degradation. The large uncleaved multimers lead to abnormal platelet ____ resulting in microthrombi
ADAMTS13; vWF; adhesion
The decreased ADAMTS13 seen in TTP is usually due to an ______ most commonly see in female/male adults/children.
acquired autoantibody; female; adults
Hemolytic uremic syndrome (HUS) is due to ____ damage by ___ or ____. It is classically seen in adults/children with _____, which results from exposure to ____.
endothelial; drugs; infxn; children; E coli O157:H7 dysentery; undercooked beef
In HUS, E coli O157:H7 ____ damages ___ cells resulting in platelet microthrombi.
verotoxin; endothelial
In which disorder resulting in microangiopathic hemolytic anemia is it more common to see renal insufficiency?
HUS (thrombi involve vessels of the kidney)
In which disorder resulting in microangiopathic hemolytic anemia is it more common to see CNS abnormalities?
TTP (thrombi involve vessels of the CNS)
Name the 5 clinical finding of HUS and TTP
1) skin/mucosal bleeding (plt micro thrombi use up plts); 2) microangiopathic hemolytic anemia (sheering of RBCs due to micro thrombi); 3) fever; 4) renal insufficiency (thrombi in kidney); 5) CNS abnormalities (thrombi in vessels of CNS)
Lab findings in microangiopathic hemolytic anemia include high/normal/low platelet count; H/N/L bleeding time; H/N/L PT/PTT; H/N/L RBCs; H/N/L megakaryocytes
low; high (since low plts); normal (coagulation cascade not activated); low (anemia with schistocytes); high (compensating)
Name four instances of qualitative platelet disorders
Bernard Soulier syndrome (GPIb defic); Glanzmann thrombasthenia (GPIIb/GPIIIa defic); aspirin (inactivates COX –> TXA2); uremia (plt funct)
_____ is a qualitative platelet disorder due to a genetic deficiency in GPIb. ____ is impaired. Blood smear shows mild thrombocytopenia with ___ platelets
Bernard-Soulier syndrome; platelet adhesion; enlarged
____ is due to a genetic GPIIb/IIIa deficiency. ____ is impaired.
Glanzmann thrombasthenia; platelet aggregation
Aspirin reversibly/irreversibly inactivates ____, leading to lack of ___, which impairs ____.
irreversibly; COX; thromboxane A2; platelet aggregation
____ disrupts platelet function and both ____ and ____ are impaired.
Uremia; adhesion; aggregation
In secondary hemostasis, the coagulation cascade generates ____, which converts ___ in the weak platelet plug to ____, which is then cross-linked, yielding a stable ____. Factors of the coagulation cascade are produced by the ____ in an active/inactive state.
thrombin; fibrinogen; fibrin; platelet-fibrin thrmobus; liver; inactive
Activation of coagulation cascade factors requires these three things.
exposure to an activating substance; phospholipid surface of platelets (since rxn occurs on platelet surface); calcium (derived from plt dense granules)
____ activates factor VII (intrinsic/extrinsic pathway)
Tissue thromboplastin; extrinsic
____ activates factor XII (intrinsic/extrinsic pathway)
sub endothelial collagen; intrinsic
Disorders of secondary hemostasis are usually due to ___ abnormalities. Clinical features include ____ into muscles and joints and ____ after surgical procedures (circumcision and wisdom tooth extraction).
factor; deep tissue bleeding; rebleeding
Prothrombin time (PT) measures intrinsic/extrinsic (factor(s) ___) and common (factors ____) pathways of the coagulation cascade
extrinsic; 7;
2, 5, 10 and fibrinogen
Partial thromboplastin time (PTT) measures intrinsic/extrinsic (factor(s) ___) and common (factors ____) pathways of the coagulation cascade
intrinsic; 12, 11, 9, 8
2, 5, 10 and fibrinogen
____ is a genetic factor VIII deficiency. It has ____ pattern of inheritance, though it can arise de novo.
Hemophilia A; x-linked recessive (so seen mostly in males)
Hemophilia A presents with ___, ___, and ___ bleeding (classic of 2ndary hemostasis disorders). Lab findings include H/N/L PTT, H/N/L PT, H/N/L F8, H/N/L platelet count and H/N/L bleeding time. Tx involves ____.
deep tissue, joint, post surgical (severity depends on degree of deficiency); High PTT; normal PT; low F8; normal plt count (it has no effect on plts); normal bleeding time; recombinant F8
Which disease has a genetic factor IX deficiency and what does it resemble?
Hemophilia B (aka Christmas disease); resembles hemophilia A except FIX levels are decreased instead of F8
In coagulation factor inhibitor, there is a ___ against a coagulation factor resulting in impaired ____. Anti-factor ___ is most common.
acquired antibody; factor function; 8
clinically similar to hemophilia A
How do you tell the difference between coagulation factor inhibitor and hemophilia A?
Mixing study: PTT does not correct upon mixing normal plasma w/pt’s plasma due to inhibitor (in hemophilia A, PTT does correct)
What is the most common inherited coagulation disorder, and what is the most common type of inheritance?
Von Willebrand Disease; autosomal dominant (decreased vWF)
there are multiple subtypes, causing both quantitative and qualitative defects - most common is above
Von willebrand disease presents with mild __ and __ bleeding, since low vWF impairs platelet ___. Tx is ___, which increases vWF release from ___ of ___ cells
mucosal; skin; adhesion; desmopressin (ADH analog); Weibel Palade bodies; endothelial
Lab findings for Von Willebrand disease include H/N/L bleeding time, H/N/L PTT, H/N/L PT. And what is seen on the ristocetin test?
high bt; high PTT (since vWF normally stabilized F8); normal PT; abnormal ristocetin test
In the ristocetin test, ristocetin induces platelet agglutination by causing __ to bind platelet ___. With a lack of the former –> impaired agglutination –> abnormal test.
vWF; GPIb
vWF can stabilize coagulation cascade factor ____. Without it, you see a decreased half life of the factor
8
Vitamin K is activated by ___ in the ___. Activated vitamin K ____ factors ___ and proteins ___ (this is needed for factor function).
epoxide reductase (coumadin blocks this enzyme); liver; gamma carboxylates; 2, 7, 9, and 10; C and S (defic disrupts funct of multiple coag factors)
Vitamin K deficiency occurs in these three cases.
Newborns (lack of GI colonization by vit K producing bacteria –> give injection to prevent hemorrhage); long term antibiotic therapy (can kill GI bacteria); malabsorption (leads to deficiency of fat soluble vit = DEAK)
Liver failure can cause abnormal secondary hemostasis because of decreased __ and __ of coagulation factors. The effect of liver failure on coagulation is followed using __
production; activation (decreased activation of vitamin K by epoxide reductase); PT (makes sense since vit K is involved more in activating PT factors - coumadin effect is seen on PT factors)
The heparin effect is measured using ___.
PTT (HEP effect –> 3 letters like PTT)
The coumadin effect is measured using ___.
PT (coumadin blocks epoxide reductase, involved in activating 2, 7, and 10 (also 9))
___ can cause abnormal secondary hemostasis by diluting coagulation factors resulting in a relative deficiency
large volume transfusion
___ is platelet destruction that arises secondary to heparin therapy. Caused when the pt develops ___ against Heparin - ___ complex. This may lead to activation of remaining platelets leading to ___.
Heparin-Induced Thrombocytopenia (HIT); IgG autoantibodies; platelet factor 4; thrombosis
___ is pathologic activation of the coagulation cascade. The widespread micro thrombi results in __ and __. Consumption of platelets and factors results in ___, especially from ___ sites and ___ surfaces.
Disseminated Intravascular Coagulation (DIC); ischemia; infarction; bleeding; IV; mucosal (bleeding from body orifices)
Name the 5 disease processes that classically cause DIC and what about it activates coagulation.
Obstetric complications (tissue thromboplastin in the amniotic fluid activates it); Sepsis (endotoxins from bacterial wall and cytokines induce endothelial cells to make tissue factor); Adenocarcinoma (mucin activates coag); APL (primary granules (form Auer rods) activate coag); Rattlesnake bite (venom)
DIC caused by sepsis is seen especially with these two bacterial infections and these two cytokines.
E coli or N meningitidis; TNF and IL-1
Lab findings for DIC include H/N/L platelet count, H/N/L PT, H/N/L PTT, H/N/L fibrinogen. Name two other common lab findings
low platelet count (plts are consumed); high PT and PTT (factors are consumed); low fibrinogen (consumed since lots of clots); microangiopathic hemolytic anemia (shearing of RBCs passing thrombi); elevated fibrin split products (esp D-dimer)
What is the best screening test for DIC?
elevated D-dimer (caused by lysing of clots - derived from splitting of cross-linked fibrin, not fibrinogen!)
Tx for DIC involves these three things
treating the underlying cause; transfusion of blood product; cryoprecipitate (contains coag factors)
Normal ___ removes thrombus after damaged vessel heals. ___ converts plasminogen to plasmin, which then cleaves ___ and ___, destroys ___, and blocks ____. ___ inactivates plasmin.
fibrinolysis; tissue plasminogen activator (tPA); fibrin; serum fibrinogen; coagulation factors; platelet aggregation (plasmin shuts down ability to form a clot AND lyses the already existing clots); alpha2-antiplasmin
Disorders of fibrinolysis are due to ____ resulting in excessive cleavage of ___. Name two examples and how they cause it.
plasmin overactivity; serum fibrinogen; Radical prostatectomy (release of urokinase activates plasmin); cirrhosis of liver (reduced production of alpha2-antiplasmin)
How do you tell apart disorders of fibrinolysis and DIC when both present with bleeding?
disorders of fibrinolysis have a normal platelet count and D-dimers are not formed since fibrin thrombi are absent (DIC has decreased plts and elevated D-dimer_
Lab findings of disorders of fibrinolysis include H/N/L PT, H/N/L PTT, H/N/L bleeding time, H/N/L plt count. You also see increased ____ with/without D-dimers.
high PT and PTT (plasmin destroys coag factors); high bleeding time (plasmin block plt aggregation); normal plt count; fibrinogen split products; without
In disorders of fibrinolysis, serum fibrinogen is lysed, but D-dimers are not formed since ___ are absent. Tx is ___, which blocks activation of ____.
fibrin thrombi; aminocaproic acid; plasminogen
