Term
| what is the normal, risk of post-traumatic bleeding, and risk of spontaneous bleeding number of platelets |
|
Definition
150000-450000 platelet/ul is normal
20000-50000 increased risk of post trauma bleeding
<20000 risk of spontaenous bleeding |
|
|
Term
| what does prothrombin time assess 7 |
|
Definition
extrinsic and common pathways
factors VII, V, II, I
warfarin therapy |
|
|
Term
| what does partial thromboplastin time assess 11 |
|
Definition
intrinsic and common pathways
factors XII, XI, IX, VIII, X, V, II, I
heparin therapy |
|
|
Term
| what does bleeding time measure |
|
Definition
|
|
Term
| what does fibrin split products measure |
|
Definition
| cleavage of fibrin or fibrinogen |
|
|
Term
|
Definition
| clevage of fibrin (htey hold fibrin together) |
|
|
Term
| what do factor levels measure |
|
Definition
| individual factor activity |
|
|
Term
| where and from what are platelets made |
|
Definition
megakaryocytes
in the marroe |
|
|
Term
| what are 3 ways platelet production can be stopped in the marrow |
|
Definition
marrow disease
impaired platelet production
ineffective megakaryopoiesis |
|
|
Term
| what are two marrow diseases that stop platelet production (give some examples of each) |
|
Definition
aplastic anemia: congenital, acquired
marrow infiltration: leukemia, disseminated cancer |
|
|
Term
| what are two ways to impair platelet production in the marrow, give some examples of each |
|
Definition
drugs: alcohol, thiazides, cytotoxic
infection: measles, HIV |
|
|
Term
| what is the most common hematological manifestation of HIV |
|
Definition
| impaired platelet production |
|
|
Term
| what are two things that cause ineffective megakaryopoiesis |
|
Definition
megaloblastic anemia
paroxysmal nocturnal hemoglobinuria |
|
|
Term
| explain the process of the formation of a primary platelet plug |
|
Definition
vessel damage
vasoconstriction: neural stimulation tells endothelial cells to release endothelian
vWF: released from subendothelial collagen webiel palate bodies when exposed during damage
platelets bind vWP with GP1b receptor (adhesion) then degranulate "releasing action" |
|
|
Term
| what are the 6 things platelets release upon activation via vWF |
|
Definition
ADP
fibrinogen
phospholipase A2
serotonin
platelet factor 4
platelet derived GF |
|
|
Term
|
Definition
| causes platelets to express GP IIb/IIIa allowing for aggregation |
|
|
Term
|
Definition
| links platelets do eachother |
|
|
Term
| what does phospholipase A2 released from platelets do |
|
Definition
combines with cyclooxygenase, thromboxane synthase, and arachadonic acid making...
cyclic endoperoxidase and THROMBOXANE A2 which recruits more platelets |
|
|
Term
| what does serotonin released from platelets do |
|
Definition
| causes vasospasm in coronary vessels |
|
|
Term
| what does platelet factor 4 do |
|
Definition
| glycoprotein that neutralizes anticoagulation of heparin |
|
|
Term
| what does platelet derived GF do |
|
Definition
| mitogen that initiates smooth muscle cell proliferation causing athlerogenesis |
|
|
Term
| why do we need secondary hemostasis if we have a platelet plug |
|
Definition
| platelet plugs are too weak |
|
|
Term
| what are the two categories of disorders of primary hemostasis |
|
Definition
| quantative and qualitative |
|
|
Term
| what are the signs of a quantative platlet disorder 13 |
|
Definition
skin bleeding: petechiae, purpura, ecchymosis
bleeding: easy bruising, epistaxia, hemoptysis, GI bleeds, hematuria, menorrhagia
intracranial bleeding: when severe
normal PT/PTT
thrombocytopenia via consumptive coagulopathy
prolonged bleeding time |
|
|
Term
| what are signs of a qualitative platelet disorder 7 |
|
Definition
bleeding: easy bruising, nose bleeds, excess bleeding from trauma, menorrhagia
PT/PTT normal
bleeding time prolonged
thrombocytopenia |
|
|
Term
| what are 6 diseases or conditions that cause quantitative primary hemostasis disorders |
|
Definition
- increased vessel fragility
- systemic conditions activate or damage endothelial cells
- immune thrombocytopenia purpura (ITP)
- thrombotic microangiopathies
- immune destruction
- non-immunologic other |
|
|
Term
| what are the 2 throbotic microangiopathies |
|
Definition
thrombotic thrombocytopenia purpura (TPP)
hemolytic uremic syndrome (HUS) |
|
|
Term
| what are 2 causes of qualitative platelet disorders |
|
Definition
|
|
Term
| 11 causes of increased vessel fragility |
|
Definition
scurvy
amyloidosis
chronic glucicorticoids
inherited CT disorders
infection
hypersensitivity vasculitides
meningococcemia
infective endocarditis
rickettsia
typhoid
henoch-schonlein purpura |
|
|
Term
| 3 systemic conditions that activate or damage endothelial cells |
|
Definition
paraxodical consumptive coagulopathy
severe bleeding |
|
|
Term
| cause of immune thrombocytopenic purpura in adults |
|
Definition
autoimmune platelet IgG to GP IIb/IIIa or GPI made in spleen
bound platelets are consumed by macrophages in the spleen causing thrombocytopenia
usually due to SLE |
|
|
Term
| immune thrombocytopenic purpura cause in kids |
|
Definition
occurs weeks after a viral infection
resolves in a few weeks |
|
|
Term
| immune thrombocytopenic purpura signs 3 |
|
Definition
pregnancy: short lived thrombocytopenia in offspring
intrecerebral and subarachnoid hemorrhages
increased megakaryocytes on marrow biopsy |
|
|
Term
| tx immune thrombocytopenic purpura 3 |
|
Definition
steroids: kids respond well, adults often relapse
IViG: short lived
splenectomy: eliminate source of AB and site of destruction of platelets |
|
|
Term
| general signs of a thrombocytic microangiopathy 4 |
|
Definition
microangiopathic hemolytic anemia
fever
anemia with schistocytes
increased megakatyocytes |
|
|
Term
| cause of thrombotic thrombocytopanie purpura |
|
Definition
autoantibody to metalloprotease ADAMSTS12 stops breaking of vWF into monomeres causing abnormal platelet adhesion
when RBC pass they shear making schistocyte causing microangiopathic hemolytic anemia
damage from RBC causes consumptive coagulopathy and thrombocytopenia |
|
|
Term
| 3 signs specific to thrombotic thrombocytopenia purpura |
|
Definition
CNS abnormalities
renal failure
fever |
|
|
Term
| TX thrombotic thrombocytopena purpura |
|
Definition
plasma exchange/plasmaphoresis (removes autoantibody(
80% successful |
|
|
Term
| cause of hemolytic uremic syndrome |
|
Definition
consumption of E. coli 0517h7 that releases shiga like toxin damages endothelial cells in kidney and brain allowing for microthrombi
this leads to RBC lysis on thrombi causing schistocytes and microangiopathic hemolytic anemia
damage from shiga like toxin and sheared RBC causes endothelial damage and consumptive coagulopathy and thrombocytopenia |
|
|
Term
| 2 signs specific to hemolytic uremic syndrome |
|
Definition
dysentery: mucous diarrhea
renal insufficiency |
|
|
Term
| prognosis of hemolytic uremic syndrome |
|
Definition
| all is reversible except for renal damage |
|
|
Term
| what are causes for immune destruction of platelets 5 |
|
Definition
isoimmune: post transfusion, neonatal
infection: mono, HIV, CMV |
|
|
Term
| what are causes for non-immunologic "other" destruction or removal of platelets 3 |
|
Definition
giant hemangioma
sequestration: hypersplenism
dilutional: HIV |
|
|
Term
| how does aspirin decrease quality of platelets function |
|
Definition
| irreversibly inactivate cyclooxygenase decreasing thromboxane A2 production and thus decreasing aggregation |
|
|
Term
| how does uremia decrease quality of platelet function |
|
Definition
| poor kidney function causes N to build up in body and cause adhesion and aggregation disorders |
|
|
Term
| where are clotting factors made |
|
Definition
| made in liver and released inactive into the blood |
|
|
Term
| how are clotting factors activated 3 |
|
Definition
activating substance
phospholipid surface (platelets)
calcium |
|
|
Term
| what is the function of the extrinsic pathway of coagulation |
|
Definition
|
|
Term
| what is the function of the intrinsic pathway of coagulation |
|
Definition
| fibrin growth and maintenance |
|
|
Term
| how is the intrinsic pathway of coagulation initiated |
|
Definition
| factor XII (hageman) comes in contact with collagen and is converted to XIIA |
|
|
Term
| how is the extrinsic pathway of coagulation initiated |
|
Definition
| tissue factor (III) released via tissue injury comes in contact with factor VII (stable) and with the help of Ca and K is turned into VIIA |
|
|
Term
| what factors and cofactors have a role in the intrinsic pathway of coagulation 12 |
|
Definition
XII
XI
IX
X
II
I
IV (calcium)
VII
K (potassium)
XIII (fibrin stabilizing factor)
V (labile)
PF3 |
|
|
Term
| what factors and cofactors have a role in the extrinsic pathway of coagulation |
|
Definition
III (tissue factor)
VII (stable)
X
II
I
XII (fibrin stabilizing)
PF3
V (labile)
IV (calcium)
K (potassium) |
|
|
Term
| explain the coagulation cascade once it converges to the end |
|
Definition
Xa converts prothrombin (II) to thrombin (IIA) using V, Ca, PF3, and K
thrombin (IIA) converts fibrinogen (I) into fibrin (IA) using XIII and Ca |
|
|
Term
| explain the extrinsic pathway up until the conversion |
|
Definition
VII (Stable) is converted to VIIA using tissue factor (III), Ca, and K
VIIA converts X to Xa using Ca |
|
|
Term
| explain the intrinsic pathway up until the conversion |
|
Definition
collagen turns XII into XIIA
XIIA turns XI into XIA
XIA turns IX (christmas) into IXA using VII, Ca, K
IXA turns X into XA using Ca and K |
|
|
Term
| what are the clinical signs of a disease of secondary hemostasis 7 |
|
Definition
deep tissue bleeding into muscles and joints
easy bruising
deep tissue hematoma
lower extremity joint hemorrhages (hemoarthoses)
rebleeding after surgery
PTT/PT prolonged
bleeding time normal |
|
|
Term
| what are 5 diseases of secondary hemostasis |
|
Definition
hemophilia A- most common hereditary disorder WITH SERIOUS BLEEDING
hemophelia B / christmas disease
coagulation factor inhibitor
vitamin K deficiency
parenchymal liver disease |
|
|
Term
| cause of hemophelia a and how is severity determined |
|
Definition
X-linked or 30% sporatic mutation in factor VIII
severe <1% VIII
moderate 1-5% VIII
mold >5% VIII |
|
|
Term
|
Definition
easy bruising
massive hemorrhages after trauma or operation
hemarthroses: joint bleeds that progress to deformities
NO petechiae |
|
|
Term
| hemophelia A: PTT, PT, platelet count, bleeding time |
|
Definition
increased PTT (improves with normal serum)
normal PT
normal platelet count
normal bleeding time
decreased factor VIII |
|
|
Term
|
Definition
| recombinant factor VIII infusion |
|
|
Term
| prognosis of hemophelia A |
|
Definition
| 15% develop neutralizing antibodies against VIII which is most severe form |
|
|
Term
|
Definition
| x-linked factor IX deficiency resembling hemophelia A |
|
|
Term
| hemophelia B: PTT, bleeding time, PT |
|
Definition
PTT prolonged
PT normal
bleeding time normal |
|
|
Term
|
Definition
|
|
Term
| cause of coagulation factor inhibitor of clotting |
|
Definition
| acquired antibody against coafulation factor impairs function (usually VIII) |
|
|
Term
| coagulation factor inhibitor of clotting: PTT, PT |
|
Definition
PT normal (usually, depends on factor)
PTT abnormal, dosent correct with normal serum addition |
|
|
Term
| how is vitamin K acquired and used for clotting |
|
Definition
generated in gut bacteria
absorbed in liver
activated by epoxide reductase
gamma carboxylates factors II, VII, IX, X |
|
|
Term
| what causes vitamin K deficiency |
|
Definition
abnormalities in bacteria
decreased vitamin K uptake
often in newborns or people on antibiotics |
|
|
Term
| why does parenchymal liver disease affect clotting |
|
Definition
decreased production of coagulation factors
decreased production of epoxide reductase so vitamin K isnt activated |
|
|
Term
| signs of parenchymal liver disease caused bleeding disorder |
|
Definition
|
|
Term
| what are 3 disease that affect primary and secondary hematostasis |
|
Definition
von willebrand disease - most common inherited coagulation disorder
disseminated intravascular coagulation
heparin induced thrombocytopenia (HIT) |
|
|
Term
| in general what is the cause of vWF diseae |
|
Definition
AD genetic vWF deficiency causes problems with platelet adhesion and factor VII stabilization
does not cause clinical signs of secondary hematostasis |
|
|
Term
| what are the 4 types of vWF disease |
|
Definition
|
|
Term
| what are the causes of the 4 types of vWF disease |
|
Definition
1. AD (classic) reduced quantity of vWF and decreased factor VIII levels
2. high moleculear weigh multimeres not made and their most active causing a qualitative vWF deficiency
2b: abnormal HMWM made but removed causing mild thrombocytopenia
3. homozogous inheritance causes loss of vWF and factor VIII |
|
|
Term
| signs of the 4 types of vWF disease |
|
Definition
1. not clinically significant
2a. qualititive vWF deficiency
2b. mild thrombocytopenia
3. resembles hemophelia |
|
|
Term
|
Definition
spontaneous bleeding from mucous membranes, wounds, menorrhagia
prolonged bleeding time |
|
|
Term
| vWF disease: bleeding time, PTT, PT, other indicating tests 2 |
|
Definition
increased bleeding time
increased PTT (vWF stabilizes VIII)
normal PT
abnormal risocertin test
decreased VIII |
|
|
Term
| why is risocertin associated with vWF |
|
Definition
| pormotes vWF platelet agglutination, binding of vWF to GP1b |
|
|
Term
|
Definition
desmopressin
increases release of vWF from weible palade bodies in endothelial cells |
|
|
Term
| what are the categories of causes of DIC 15 |
|
Definition
obstretic complications
sepsis
neoplasm
endothelial injury
rattlesnake bite
hemangioma
vasculitis
aortic aneurysm
liver disease
heat stroke
burn
surgery
shock
trauma
acute intravascular hemolysis |
|
|
Term
| why do obstretic complicatins cause DIC, give 5 examples |
|
Definition
amniotic fluid contains tissue thromboplastin and activates coagulation cascade
abruptoplacentae
retained dead featus
septic abruption
toxemia
amniotic fluid embolism |
|
|
Term
| why does sepsis cause DIC, give 7 examples |
|
Definition
microbe toxins induce tissue factor release from monocytes which releases IL1 and TNF which increase THROMBOMODULIN
GNB, GPB, meningococcemia, malaria, RMSF, histoplasmosis, aspergillosis |
|
|
Term
| why does neoplasm cause DIC, give 5 examples |
|
Definition
express tissue factor III
pancreas, prostate, lung, stomach, acute promyelocytic leuemia |
|
|
Term
| what can cause widespread endothelial injury causing DIC 5 |
|
Definition
SLE
heat stroke
burn injury
meningitis
rickettsiae |
|
|
Term
| why does rattlesnake venom cause DIC |
|
Definition
|
|
Term
| why does traima cause DIC |
|
Definition
| brain releases phospholipids and fat and activate intrinsic cascade |
|
|
Term
| explain the MOA of DIC causing complications 3 |
|
Definition
widespread damage causes widespread microthrombi and FIBRIN DEPOSITION which causes ischemia and infarction
consumptive coagulopathy: formation of thrombi uses platelets, factors, fibrin leading to BLEEDING DIATHESIS
MICROANGIOPATHIC HEMOLYTIC ANEMIA: hemolysis of RBC in vessel narrowings |
|
|
Term
|
Definition
bleeding: prolonged, post-partum, petechiae/ecchymosis, GI/GU hemorrhages
thrombosis: abnormal clotting in microcirculation (minimal symptoms)
systemic: shock, acute real failure, dyspena, cyanosis, convulsions, coma
WATERHOUSE FRIDERISCHEN SYNDROME: microinfarcts in brain, neurological signs
SEEHAN POST PARTUM PITUITARY NECROSIS: eclampsia is hypercoagulable state and leads to thrombi in placenta, liver, kidney, brain and PITUITARY |
|
|
Term
| DIC: RBC changes, platelet count, PT, PTT, fibrinogen levels |
|
Definition
MICROANGIOPATHIC HEMOLYTIC ANEMIA: RBC sheared by thrombi
THROMBOCYTOPENIA
INCREASED PT AND PTT: consumed by all factors
decreased fibrinogen: busy working on thrombi
elevated D-dimers (fibrin split products): removal of clot after healing causes lysis of cross linked fibrin released D-dimers |
|
|
Term
|
Definition
|
|
Term
| cause of heparin induced thrombocytopenia |
|
Definition
| after 1-2wk heparin forms complex on platelet factor IV and body forms IgG autoantibodies that cause consumption of platelets by spleen |
|
|
Term
| what are the two types of HIT and what is the difference |
|
Definition
HIT1: platelets decrease due to non-immunologic mechanisms limited to 2-4d
HIT2: becomes life threatning(white clot syndrome) lasts 6-12d |
|
|
Term
|
Definition
platelet destruction causes fragmented platelets to enter circulation and allow thrombosis
arterial and venous thrombosis |
|
|
Term
|
Definition
DC heparin
begin lepirudin or warfarin
reoccurs with heparin use |
|
|
Term
| what 5 things does the endothelial cells release/have that do fibrinolysis |
|
Definition
t-PA/plasminogen
heparin like proteoglycans
prostacyclin
transmural negative charge
protein C activation |
|
|
Term
|
Definition
| turns plasminogen into plasmin |
|
|
Term
|
Definition
cleaves fibrin and serum fibrinogen
destories coagulation factors
blocks platelet aggregation |
|
|
Term
| what deactivates plasmin 3 |
|
Definition
a2 antiplasmin: degrades plasminogen when plasmin is unbound
PA-1 and urokinase tissue plasminogen activator (sCU-PA): endothelium degrades tPA |
|
|
Term
| what does prostacyclin do |
|
Definition
platelet inhibitor
binds and increases cAMP > activats phospholipase A2 > cyclooxygenase > prostacyclin synthase activated on membrane lipids > prostacyclin |
|
|
Term
| how does the transmural negative charge of entothelial cells affect clotting |
|
Definition
| helps fibrinolysis by preventing adhesion of platelets |
|
|
Term
| proteiin C activation role in clotting |
|
Definition
| degrades coagulation factors (thrombin modification with thrombomodulin) |
|
|
Term
| what are 2 diseases that affect fibrinolysis |
|
Definition
radial prostectomy
liver cirrhosis |
|
|
Term
| how does radial prostectomy affect clotting |
|
Definition
| release of urokinase in procedure activates plasmin which breaks down clotting factors and fibrinogen causing bleeding |
|
|
Term
| how does liver cirrhosis affect clotting |
|
Definition
| a2 antiplasmin is not produced and plasmin breaks down clotting factors and fibrinogen causing bleeding |
|
|
Term
| tx of liver cirrhosis decreased a2-antiplasmin |
|
Definition
| aminocaproic acid: blocks activation of plasminogen |
|
|
Term
| signs of liver cirrhosis decreased a2-antiplasmin |
|
Definition
|
|
Term
| liver cirrhosis decreased a2-antiplasmin: PT, PTT, bleeding time, platelet count, fibrinogen levels |
|
Definition
PT/PTT increased: clevage of clotting factors
increased bleeding time: inhibition of platelet aggregation
platelet count normal: not using them to make thrombi
increased fibrinogen split products but NO D-DIMER: there was no thrombus, no D dimer |
|
|
