Hemostasis + Disorders Flashcards
What are the 4 steps in primary hemostasis and how are they mediated? What does vWF bind? Which receptors? Where is vWF stored/made? Where is ADP released from? What does it do? What does TXA2 do and how is it made? What does fibrinogen bind? How is primary hemostasis stabilized?
Transient Vasoconstriction-neural reflex and endothelin
Platelet adhesion to disrupted vessel
vWF binds exposed SEC. It also binds platelets at the GPIb receptor
VWF is made in weibel palade bodies of endothelial cells and alpha granules of platelets
Platelet degranulation-adhesion causes a shape change leading to degranulation
ADP is released from dense granules on platelets and it causes GPIIb/IIIa to be promoted
TXA2 is synth by COX and causes platelet aggregation
Platelet aggregation
GPIIb/IIIa binds to fibrinogen forming a weak plug that is eventually stabilized by secondary hemostasis
What are the clinical features of primary hemostasis? What are some useful lab studies?
Mucosal bleeding: epistaxis, hemoptysis, GI bleeding, hematuria, and menorrhagia
skin bleeding: petechiae (quantitative only), purpura, ecchymoses
Platelet count
Bleeding time-increased in both quant and qual.
Blood smear-number and size of platelets
Bone marrow biopsy-assesses megakaryocytes
Ristocetin test-causes primary hemostasis to occur by causing GPIb to bind vWF. Will not cause clotting if either of those are defective or absent.
What is ITP? Pathophys? What is the acute form like? What is the chronic form like? Cause of each? What lab findings are there in ITP? What is the first line treatment? How do people lrespond? What is done if taht doesn’t work?
Immune thrombocytopenic purpura
IgG against platelet antigens. antibodies produced by plasma cells in spleen. Platelets then destroyed by splenic macrophages (thrombocytopenia)
Acute form: Children after viral illness or immunization, usually self limited
Chronic form: Women of child bearing age, primary or secondary
Decr. platelet count
What is MAHA? What is the pathophys? What diseases is it associated with? Clinical findings? Lab findings? Treatment?
formation of platelet microthrombi in small vessels which uses up platelets and shears RBCs (schistocytes)
TTP and HUS
Skin and mucosal bleeding MAHA Fever Renal insufficiency (moreso in HUS) CNS abnormalities (moreso in TTP)
Thrombocytopenia with incr. bleeding time
Normal Pt/Ptt
Anemia with schistocytes
Incr.megakaryocytes
Plasmapheresis and corticosteroids (mainly for TTP)
What is the pathophys of TTP? Pathophys of HUS?
Autoantibody against ADAMTS13 (usually in women) causes it be decreased.
It is unable to cleave some of the multimers of vWF which results in abnormal platelet adhesion leading to microthrombi.
Endothelial damage by drugs on infection
E coli O157:H7 (undercooked beeef)
Verotoxin damages endothelial cells resulting in microthrombi
What is the pathophys of Bernard-soulier? What is seen on blood smear? What is the pathophys of glanzmann thrombastenia? How does aspirin impair platelet aggregation? How is primary hemostasis impaired in uremia?
Genetic GPIb deficiency
Blood smear shows mild thrombocytopenia with enlarged platelets
GPIIb/IIIa deficiency
Inactivates COX-no TXA2
Adhesion and aggregation impaired.
What does erythrocytosis mean? Anisocytosis? Poilocytosis? What is a reticulocyte? What does it reflect?
Incr. hematocrit, polycythemia
Varying sizes
Varying shapes
Immature rBC=reflects erythroid proliferation.
Waht is the lifespan of thrombocytes? What is contained in dense granules? alpha granules? Where are 1/3 of platelets stored?
8-10 days
Ca, ADP
vWF, fibrinogen
spleen
Describe the steps of secondary hemostasis (both pathways) including the various factors? Where are the factors produced? What are the 3 things required to activate them (both pathways) ?
Activated after exposure to an activating substance (SEC activates FXII in the intrinsic pathway and Tissue thromboplastin activates factor VII in extrinsic pathway)
Phospholipid surface of platlets
Calcium (from dense granules)
XII to XI to IX to X to II to I
VII to X to II to I
FII (thrombin) also activates FVIII which works with FIX to make it more efficient at converting X
activates V which makes X more efficient at converting II
Activates XIII which crosslinks fibrin forming mesh.
What are some clnical features of secondary hemostasis? Lab studies used?
deep tissue bleeding into muscles and joints nd rebleeding after surgical procedures.
PT=Extrinsic
PTT=Intrinsic
What is hemophilia A pathophys? Presentation? Lab findings? Treatment? What hemophilia B? Same questions? What is a coag factor inhibitor? Same questions? How can it be differentiated from hemo A?
FVIII defic.
Deep tissue, joint bleeding and rebleeding
Incr. PTT, normal PT
Decr. FVIII
Normal platelet count and bleeding time
Recomb. FVIII
FIX defic, otherwise very similar to A.
Antibody against a coag factor, usually FVIII.
clinically looks like Hemo A
PTT Not corrected by mixing plasma with normal plasma
What is the pathophys of Von willebrand disease? How does it present? Lab findings? What is the treatment? Mechanism?
vWF defic, can cause quant. or qual. disorders.
Impaired vWF prevents platelet adhesion.
Normally, vWF stabilizes FVIII, but it can’t do that when impaired.
Mild mucosal and skin bleeding (no deep tissue)
Incr. bleeding time
Incr. PTT, normal PT
Abnormal ristocetin
Desmoressin-incr. vWF release from WP podies
How and where is vitamin K activated? What is the function of vit. k in coag? When does defic occur?
Epoxide reductase in liver
gamma carboxylates factors II, VII, IX, X, protein C/S.
Newborns, long term antibiotic therapy, malabsorption
How does liver failure lead to abnormal secondary hemostasis? Large volume transfusion?
Liver=Decr. production of coag factors and decr. activation of vit. K. Followed using PT
Large volume transfusion dilutes coag factors.
What is heparin induced thrombocytopenia?
platelet destruction secondary to heparin therapy
Fragments of destroyed platelets may activate other platelets leading to thrombosis
What is DIC? Clinical results? 5 causes? 5 lab findings? Treatment?
pathogic activation of coag cascade leads to widespread microthrombi w/ ischemia and infarction.
The microthrombri use up platelets and factors resuling in bleeding from IV sites a nd mucosal surfaces
Obstetric omplications (tissue thromboplastin in amnio Sepsis (E. coli and N menin)=endotoxins from bacterial wall and cytokines (TNF and IL-1) induced endothelial cells to amke tissue factor Adenocarcinoma=mucin acute promyelocytic leukemia=primary granules rattlesnake bite=venom
decr. platelets Incr. PT/PTT Decr.fibrinogen MAHA Elevated fibrin split products (D Dimer=not produced in slitting of fibrinogen)
Address underling cause; give blood products, cryoprecipitate
How does normal fibrinolysis function? What causes disorders of fibrinolysis? Examples? How do they present? Lab findings? Treatment? Mechanism?
Tissue plasminogen activator (tPA) converts plasminogen to plasmin
Plasmin cleaves fibrin and serum fibrinogen;destroys coag factors and blocks platelet aggregation
Alpha 2 antiplasmin inactivates plasmin
PLasmin overactivity
Radical prostatectomy: urokinase activates plasmin
Cirrhosis of liver=decr. alpha 2 antiplasmin
Increased bleeding (like DIC)
Incr. PT/PTT
Incr. bleeding time with normal platelet count
Incr. fibrinogen split products w/o D dimers
Aminocaproic acid-blocks plasmin activation
What are 3 things that lead to a disruption in blood flow? How do endothelial cells prevent thrombosis? What does ATIII do? What does thrombomodulin do? Protein C/S? What are some causes of endothelial cell damage?
Immobilization
cardiac wall dysfunction
aneurysm
Block exposure to SEC and tissue factor
Produce PGI2 and NO
Secrete heparin like molecules which augment ATIII function (inactivates FII and FX)
Secrete tPA which converts plasminogen to plasmin
Secrets thrombomodulin-redirects thrombin to activate protein C which inactivates factors V and VIII.
Atherosclerosis, vasculitis, and high levels of homocysteine
Describe how the lack of vit. b12 or folate can lead to incr. risk of thrombosis. Describe the pathophys of cystathionine beta synthase defic. How does it present?
folate circulates as methyl-THF
The methyl group is transferred to vit. b12, which allows THF to be used in production of DNA precursors.
Cobalamin transfers methyl to homocystein resulting in methionine.
Lack of Vit. B9 or cobalamin results in incr. homocysteine and thus incr. thrombocytosis.
CBS converts homocystein to cystathionine; enzyme deficiency leads to homocystein buildup
Vessel thrombosis, mental retardation, lens dislocation, and long slender fingers
What is a hypercoagulable state? How does it present? Where?
Excessive procoag and defic anti coags
Recurrent DVTs or DVT at young age
Usually in lower leg (maybe hepatic or cereral)
How does protein C and S defic lead to a hypercoag state? What does it incr. risk for when using warfarin? Why? What is factor V leidn? Prothrombin 20210A? ATIII deficiency? OCPs?
Protein C/S inactivate factors V and VIII
Warfarin blocks Protein C/S as well as pro coag factors but C/S have shorter half lives and thus are defic. first leading to a hyper coag state, but if C/S are already defic it becomes a big problem, leading to ischemia in skin or warfarin induced necrosis
mutated factor V can’t be inactivated by Protein C/S
Mutation leads to incr. production of prothrombin
ATIII defiency makes it so heparin like molecules can’t exert as great an effect b/c ATIII can’t inactivate thrombin and factor X
Estrogen incr. coag factors
What is a fat embolus associated with? Clinical manifestations? Pathophys of gas embolus? Clinical manifestation? Causes? Chronic form? Amniotic fluid embolus presentation? Characterization?
Bone fractures and soft tissue trauma
Dyspnea and petechiae on the skin over chest
Decompression sickness=rising too quickly, N2 precipitates out of blood. Joint and muscle pain and respiratory symptoms Chronic form (Caisson)=multifocal ischemic necrosis of bone May also occur in laparascopic surgery
Amniotic fluid embolus enters maternal circulation during labor or delivery
Shortness of breath, neuro sympoms, DIC
Squamous cells and keratin debris in embolus
What causes a pulmonary embolism? Why are most clinically silent? When does a pulmonary infarction occur? How does it present? When does sudden death occur? When does pulmonary hypertension occur
Usually due to a DVT of lower extremity.
Usually silient b/c lung has dual blood supply and embolus is small
Pulmonary infarction occurs if large or medium sized arter is occluded in someone with preexisting cardio compromise
Shortnes of breath, hemoptysis, pleuritic chest pain, and pleural effusion
V/Q lung scan shows mismath
Spiral CT shows a vascular filling defect
Lower extremity doppler
D-dimer elevated
Hemorrhagic wedge shaped infarct
Sudden death occurs with large saddle embolus blocking left and right pulm. arteries
Pulmonary hypertension occurs with repeated PE that are reorganized over time.
