Hemostasis Flashcards
coagulopathy
A condition characterized by impaired clotting of blood
Hypercoaguability (thrombophilia)
A condition characterized by an increased tendency toward blood clotting
Reflex vasoconstriction
1st step of primary hemostasis
2nd step of primary hemostasis
vWF line surface of disruption at subendothelial collagen, platelets bind to vWF
3rd step of primary hemostasis
Platelets activate and degranulate
Binding to vWF causes change in platelet shape -> dump mediators from granulation. Mediators are ADP and TXA2.
Platelet aggregation
4th step in primary hemostasis
Primary hemostasis
Form a weak platelet plug. Mediated by platelet wall interactions
Secondary hemostasis
Stabilizes platelet plug by forming a fibrin meshwork. Mediated by coagulation cascade.
Tertiary hemostasis
clot limitation and fibrinolysis - need to limit clot size and contain the reaction
Plasmin
In fibrinolysis, this molecule removes the thrombus by cleaving fibrin and fibrinogen, destroys coagulation factors and blocks platelet aggregation
tPA
converts plasminogen to plasmin to start fibrinolysis
Normal endothelium
Expresses proteins that inhibits platelet aggregation, act as vasodilators, facilitate the inactivation of thrombin
vWF
Line surface of endothelial disruption at subendothelial collagen. Attach to platelets
Bone marrow by megakaryocytes
Where are platelets made?
Factor VIII
vWF protects which factor
Liver
Coagulation cascade proteins are made here except VIII
VIII
Only factor made in endothelial cells
II, VII, IX, X
Vitamin K dependent factors
V, VIII, XI, XIII, platelets and fibrinogen
Thrombin activates
XIII
Enzyme that crosslinks fibrin and helps to stabilize clot, activated by thrombin
X
Active form of this factor activates thrombin, intrinsic and extrinsic pathways feed together to this factor
V and VIII
Thrombin can be an inhibitor to stop clotting cascade. Bind thrombomodulin, protein C, protein S which inactivate these factors
Antithrombin
Inhibits all the serine proteases (Xa, XIa, IXa, XIIa, VIIa) but especially thrombin
Heparin
Binds to antithrombin and makes it a much more potent inhibitor of thrombin
Works mostly on thrombin, but also XI and X. Major effect is intrinsic so PTT effects more striking
TFPI
Inhibits Xa and VIIa
PT
When extrinsic pathway is affected, this time is abnormal
PTT
When intrinsic pathway is affect, this time is abnormal
Abnormal PT
Defect in factor VII shows
Abnormal PTT
Defect in factor XII, XI, IX, or VIII shows
Abnormal PT and PTT
Defect in factor II, V, X, or fibrinogen shows
TEG (thromboelastography)
Mechanical test of clotting strength development. Assesses ability of platelets to pull the fibrin clot into a tight mesh and of desolution
Defects in primary hemostasis
Platelet problems, Von Willebrand disease
Defects in secondary hemostasis
Hemophilia, vitamin K deficiecny, anticoagulation
von Willebrand’s disease
Most common inherited bleeding disorder. Autosomal DOMINANT. Causes “mucosal” bleeding (nosebleeds, prolonged bleeding with dental work, heavy menses, easy bruising, etc) Usually type 1 is mild, but potentially a problem with major injury or surgery
Unlike most platelet problems, it is inherited, life-long, a/w family history
von willebrand testing
Measure antigen level, activity (ristocetin cofactor activity), factor VIII level, multimer assay
Petechiae, bruising, mucosal bleeding
Clinical presentation of platelet problems (primary hemostasis)
ITP
Immune reaction to platelets. Very low platelet counts, but normal bleeding time. Platelets produced are young and super functioning
VIII, IX
X-linked recessive defects in these factors (hemophilia)
XII
If defect in this factor, thrombin will still activate the next step (XI)
Hemophilia A
X-linked recessive, factor 8 deficiency
Bleeding deep and delayed
Hemophilia B
X-linked recessive, factor 9 deficiency
Bleeding deep and delayed
Acquired factor VIII inhibitor
Acquried hemophilia, antibody against this factor. Occurs most commonly in elderly patients, also seen postpartum, in rheumatologic disease, and malignancy. Presents most commonly with soft tissue bleeding
Prolonged PTT
Vitamin K deficiency
See a prolonged PT and PTT, but more commonly you will see only a prolonged PT
From a dietary deficiency (rare), antibiotics, malabsorption, newborn, and coumarins
To treat, give supplements (carefully if back on Warfarin), plasma (short term fix to get factors), and Kcentra (for emergencies)
Warfarin
Followed using the PT. Blocks recycling of vitamin K and causes deficiency
Causes of a prolonged PT
Warfarin use, liver disease, Vit K deficiency, Factor VII deficiency
Causes of a prolonged PTT
Heparin use, factor deficiency (VIII, IX, XI, XII, von willebrand (protects 8)), antiphospholipid antibody (lupus inhibitor), DIC
Lupus anticoagulant phenomenon
Prolonged phospholipid-dependent coagulation tests caused by autoantibodies against phospholipid-binding proteins- cause hypercoagulable state. Anti-phospholipid syndrome is associated with thrombosis, not bleeding (more prone to thrombosis)
In vitro phenomenon - test makes it look like a bleeding problem with prolonged PTT
In vivo they are not anticoagulants but promote thrombosis
DIC
Coagulation system is activated everywhere. From sepsis, viral hemorrhagic fevers, trauma, cancers, OB complications, toxins (rattlesnakes), vascular disorders, immunologic disorders,etc
Usually a SECONDARY disease
Intravascular deposition of fibrin leads to trombosis of small vessels (microangiopathic hemolysis), depletion of platelets and coag factors leads to bleeding
Schistocytes or helmet cells
Types of cells seen in DIC and TTP from microangiopathic hemolysis
Lab findings for DIC
Prolonged PT, PTT
Decreased platelet count and fibrinogen
Increased D- dimers***** seen here because fibrin is being cut
Abnormalities on peripheral smear (like schistocytes)
Anti-thrombin III deficiency
Most common severe inherited thrombophilic disorder. Can cause venous thrombosis and embolism
Antithrombin, Protein C, Protein S deficiencies
Uncommon causes of inherited thrombophilia associated with high thrombotic risk
Factor V Leiden
Common cause of inherited thrombophilia associated with lower thrombotic risk- mutation that keeps factor activated longer than it should be
Liver disease
Have a hard time forming clots because of loss of all factors but 8, can’t activate Vit K
ALSO have a hard time inhibiting clots so have prolonged PT and PTTs but may actually be prone to thrombosis
