TEST 2: Coagulation Flashcards
Virchow Triad
Venous stasis, vessel damage, hypercoagulable state (venous thrombus formation)
Risk factors: age, obesity, pregnancy, cancer, surgery, trauma, prolonged immobilization, genetic hypercoagulable states, meds like oral contraceptives or hormone replacement therapy
Idiopathic (or Immune) Thrombocytopenic Purpura (ITP)
Mechanism, Symptoms & NOTES
Mechanism: antibodies target and destroy platelets-> thrombocytopenia
Symptoms: Purpura, petechiae, mucosal bleeding, bruising.
Notes: more common in females, can affect kids and adults
Idiopathic (or Immune) Thrombocytopenic Purpura (ITP)
Labs & treatment
Labs: coagulation is usually normal, just low platelet count (< 100k), R/O other causes HIV/Hep C etc first.
Treatment: Observe if no bleeding, corticosteroids, IVIG, Rituximab or thrombopoietin, if intractable splenectomy.
Idiopathic (or Immune) Thrombocytopenic Purpura (ITP)
Primary vs. Secondary
Primary vs. Secondary: primary is isolated thrombocytopenia with no identifiable cause, as a diagnosis of exclusion from all other possible causes leaving autoimmune.
Secondary thrombocytopenia associated with a specific identifiable underlying condition or trigger ex. Viral infection, malignancy, other autoimmune diseases, or some drugs.
Thrombotic Thrombocytopenic Purpura (TTP)
Mechanism & Symptoms
Mechanism: severe deficiency of ADAMTS13 (enzyme that acts on von Willebrand factor) can be secondary to genetic mutations (Upsaw-Schulman Syndrome) or more commonly antibodies that inhibit that enzyme.
Symptoms: predictable symptoms stemming from thrombocytopenia, hemolytic anemia, renal dysfunction, and fever.
Thrombotic Thrombocytopenic Purpura (TTP)
Labs & treatment
Labs: Severely reduced activity of ADAMTS13 or antibody against it, thrombocytopenia, low Hgb, high LDH, high indirect bilirubin, high reticulocyte count, normal coagulation tests.
Treatment: Plasmapheresis (first line), corticosteroids, rituximab
Hemophilia A
Mechanism & symptoms
Mechanism: Factor VIII deficiency, mutation in the F8 gene
Symptoms: bleeding of knees, elbows, ankles, GI. If mild bleeding will only occur after injury/trauma/surgery. If severe spontaneous bleeding can occur.
Hemophilia A
Labs & GEMS
Labs: Normal plts, normal PT, abnormal aPTT, low factor VIII
EARLY SIGNS IN CHILDREN: easy bruising, swelling, joint redness, mouth bleeding.
By age 3-4 most kids will have experienced an episode of excessive bleeding.
Boys can often be circumcised without excessive bleeding, but this does not guarantee the absence of hemophilia.
Hemophilia B (Christmas Disease)
Mechanism & Symptoms
Mechanism: Factor IX deficiency, mutation in the F9 gene
Symptoms: bleeding of knees, elbows, ankles, GI. If mild bleeding will only occur after injury/trauma/surgery. If severe spontaneous bleeding can occur.
Hemophilia B (Christmas Disease)
Labs & GEMS
Labs: normal plts, normal PT, abnormal aPTT, low factor IX.
Gems: EARLY SIGNS IN CHILDREN: easy bruising, swelling, joint redness, mouth bleeding.
By age 3-4 most kids will have experienced an episode of excessive bleeding.
Boys can often be circumcised without excessive bleeding, but this does not guarantee the absence of hemophilia
Disseminated Intravascular Coagulation (DIC)
What is it, causes, mechanism
What: not a disease itself but a secondary effect of other medical conditions, leading to both excessive bleeding and clotting.
Causes: infection (sepsis), cancer, severe preeclampsia, placental abruption, trauma (TBI, burns, massive injury), ARDS, rhabdomyolysis, venomous snake bites, shock states, acidosis, hypoxia, fulminant liver failure, severe pancreatitis, transfusion reactions, or recreational drug use.
Mechanism: starts with endothelial damage activating clotting, simultaneously fibrinolytic system is activated, coagulation factors get depleted causing bleeding, the widespread clotting causes micro-thrombi systemically causing organ dysfunction from the disrupted blood flow.
Disseminated Intravascular Coagulation (DIC)
Symptoms, labs, treatment
Symptoms: diffuse bleeding at multiple sites with minimal trauma, petechiae, large areas of ecchymosis, organ hemorrhage, stroke, PE, necrotic skin lesions, multisystem failure, blue finger/toe syndrome
Labs: high PT/PTT, low fibrinogen, high d-dimer, low platelets
Treatment: Fix underlying cause, blood products, anticoagulants, supportive care.
Thrombus vs. embolus vs. thromboembolism
thrombus is any clot that forms in a blood vessel
embolus is a thrombus or any other debris that breaks free and travels through the blood stream
thromboembolism is a general term for traveling clots
DVT
Provoked vs unprovoked
why proximal is important?
Provoked: due to a known risk factor
Unprovoked: occurs without any identifiable risk factor
Proximal DVT: Femoral or iliac veins, considered more dangerous than smaller veins due to size, higher risk of complications (PE etc.) and increased risk of recurrence.
Protein C Deficiency
Result
Mechanism
Symptoms
GEMS
Result: natural anticoagulant
Mechanism: Inherited: (autosomal dominant) causing reduced production. Acquired: severe liver disease, DIC, warfarin
Symptoms: DVT/PE, warfarin induced necrosis
GEMS: higher risk with pregnancy, oral contraceptive, cancer, IBS
Protein S Deficiency
Result
Mechanism
Symptoms
Results: is a Cofactor for Protein C enhancing the anticoagulant effect, therefore deficiency leads to excess clotting
Mechanism: Inherited: (autosomal dominant mutation), reduced production
Symptoms: DVT/PE, recurrent miscarriages
Factor V Leiden
Mechanism
Symptoms
GEM
Mechanism:
only inherited, point mutation on factor V gene making factor Va resistant to inactivation by protein C
Symptoms: DVT/PE/Stroke
GEM: most common inherited hypercoagulable state
Antiphospholipid antibody syndrome
What it is and GEMS
Acquired autoimmune syndrome where antibodies attack plasma proteins and clotting factors
GEMS: More common in women, commonly discovered after multiple miscarriages, results in many pregnancy complications
3 Methods of Hemostasis
Vascular spasm (vasoconstriction)
Platelet plug
Coagulation cascade
Primary hemostasis vs Secondary hemostasis
Primary hemostasis= platelet plug,
Secondary hemostasis= intrinsic/extrinsic/common pathway
Intrinsic Pathway
What it is
Significant points
Clinical relevance
WHAT: activation is essential for maintaining hemostasis and preventing excessive bleeding when VESSELS ARE DAMAGED.
Significant:
started when a specific factor comes into contact with exposed collagen in a vessel wall (or negatively charged surface).
Uses many clotting factors culminating in Xa, Joins the COMMON pathway
Clinical Relevance:
deficiencies in intrinsic pathway factors (of which there are several) can lead to bleeding disorders such as Hemophilia A & B.
Extrinsic Pathway
What it is
Significant points
Clinical relevance
WHAT: typically triggered by external trauma causing blood to exit the vascular system.
Significant points:
Started with exposure to Tissue factor outside the blood stream
Also joins the COMMON pathway at factor Xa
Clinical relevance: Different starting point i.e. physical trauma, dysregulation can result in bleeding or thrombotic conditions.
Common Pathway
What it is
Significant points
Clinical relevance
What: End of intrinsic and extrinsic pathways
Significant Points: where anticoagulation mechanisms work. Examples: tissue factor pathway inhibitor, antithrombin III, protein C & S
Xa converts prothrombin to thrombin -> fibrinogen becomes fibrin -> reinforcement of platelet plug.
Clinical Relevance: Both intrinsic and extrinsic pathways lead to the common pathway where clotting and inhibition of clotting occur.
Prothrombin Time (PT)
What does it assess?
Clinical Significance?
Assess: assess extrinsic and common pathway
Prolonged could indicate deficiencies in factors, liver disease, vit K def., or anticoagulation therapy.
Activated Partial Thrombin Time (aPTT)
What does it assess?
Clinical Significance?
assess intrinsic and common pathway
Prolonged could indicate hemophilia, von Willebrand, heparin therapy, and presence of certain inhibitors (lupus anticoagulant)
Fibrinogen
What does it assess?
Clinical Significance?
converted to fibrin by thrombin in last step of coagulation cascade making stable clot
Low may indicate DIC, liver disease or conditions that cause fibrinolysis
High may indicate acute phase reactions, inflammation, pregnancy, or some cancers.
ASA
minimal effect on coagulation, mostly antiplatelet
Clopidogrel
primarily targets platelet function
Low Molecular Weight Heparin
enhances antithrombin activity (inhibits thrombin and factor Xa)
Factor Xa Inhibitors (ex. Apixaban)
decreased conversion of prothrombin to thrombin
Direct thrombin inhibitor (ex. Argatroban)
direct inhibition of thrombin preventing fibrinogen converting to fibrin.
