Coagulopathy Flashcards
Prolonged activated Partial Thromboplastin Time (aPTT)
Genetic
Hemophilia A/B
(X-linked)
Hemophilia A prolonged A PTT
Prolonged aPTT
Prolonged Bleeding time
vWF deficiency
intrinsic (8, 9, 11, or 12) pathway defect
Prolonged PT, aPTT, Bleed Time
Low Platelets
DIC
Prolonged Bleed time
Uremic platelet dysfunction
Prolonged aPTT
Heparin
Prolonged aPTT
Low Platelets
HIT
Prolonged Prothrombin (PT) slightly elevated aPTT (if at all)
Warfarin
Low Platelets
Immune Thrombocytopenia
↓ ADAMTS-13 level →
uncleaved vWF multimers →
platelet trapping & activation
Acquired (autoantibody) or hereditary
Thrombotic thrombocytopenic purpura
TTP
↑ bilirubin ↑ LDH, ↓ haptoglobin ↑ bleeding time
↓ Platelets, schistocytes, Petichiae
↑ creatinine
Thrombotic thrombocytopenic purpura
TTP
Diffuse microvascular thrombosis, causing microangiopathic hemolytic anemia
Thrombotic thrombocytopenic purpura
TTP
Vascular damage & microthrombi formation
From Shiga toxin or Escherichiacoliserotype O157:H7
Hemolytic uremic syndrome
↑ bilirubin ↑ LDH, ↓ haptoglobin ↑ bleeding time
↓ Platelets, schistocytes, Petichiae
Acute kidney injury (↑ BUN, ↑ creatinine)
Hemolytic uremic syndrome
Preceding bloody diarrhea
DIC is marked by the excessive activation of the _______ coagulation cascade, leading to the generation of thrombin and cross-linked fibrin clots.
______ is then activated to clear the intravascular thrombi; plasminogen is converted to plasmin, which _________ and generates fibrin-degradation products (eg, elevated D-dimer).
Other anticoagulant proteins (eg, protein C, protein S) are also rapidly consumed.
extrinsic (tissue factor)
Fibrinolysis
cuts the cross-linked fibrin-fibers
(Plasmin Pierces Fibrin)
Exertional heat stroke (extreme hyperthermia) and seizures increase the risk of ___
DIC
vWD is inherited in an autosomal dominant fashion with ________ and is the most common heritable bleeding disorder.
variable penetrance
Direct factor Xa inhibitors (eg, apixaban) are anticoagulants that block the ______ of factor Xa, which leads to reduced conversion of ___ to ____.
active site
prothrombin to thrombin
Warfarin inhibits vitamin K epoxide reductase, which decreases the _____ form of vitamin K and limits _____ of vitamin K–dependent coagulation factors (II, VII, IX, X).
reduced
gamma-carboxylation
Cimetidine, amiodarone, and TMP-SMX are CYP P450 inhibitors which ______, thus increasing the risk of ______.
Lowers warfarin metabolism (increases it’s effect)
bleeding
Abnormal bleeding in patients with uremia (Pt on Dialysis or with CKD/ESR disease) is due to a qualitative platelet disorder that causes prolonged ______ only!
bleeding time
Absent or ↓ factor ___ (hemophilia A)
Absent or ↓factor ___ (hemophilia B) activity
8 (Hemophilia 8-Ate)
9
Slow oozing blood after mild trauma
Hemarthrosis, intramuscular hematomas
GI/GU bleeding
Intracranial hemorrhage
Hemophilia A/B
(intrinsic Pathways defect)
Complications: hemophilic arthropathy
Low haptoglobin is a sign of
hemolytic anemia
Other associated findings include increased indirect bilirubin and lactate dehydrogenase.
Signs of ______ include easy bruisability, petechiae, and mucocutaneous hemorrhage (eg, recurrent epistaxis, gingival hemorrhage).
thrombocytopenia
PT reflects the _____ clotting pathway, which involves _____, fibrinogen, and factors II, V, VII, and X.
extrinsic
tissue factor
_____ causes dusky discoloration of the skin (similar to cyanosis), and because it is unable to carry oxygen, a state of functional anemia is induced.
However, the blood ____ of oxygen will be unchanged as it is a measure of oxygen dissolved in plasma and is unrelated to hemoglobin function.
Methemoglobinemia
partial pressure of O2
_____ is an intracellular iron-storage protein that is used as a serum marker of total body iron stores.
Ferritin
Hypersegmented neutrophils are characteristic of _______, which can be caused by folate and vitamin B12 deficiency.
megaloblastic anemias
Etoposide is a chemotherapeutic agent that inhibits the sealing activity of _________.
Treatment causes chromosomal breaks to accumulate in dividing cells, as double stranded DNA fragments, ultimately causing cell death.
topoisomerase 2
Prolonged Bleed time
Low Platelets
TPP
warfarin-induced ______, a rare complication that can occur in individuals with underlying protein C or S deficiency shortly after starting warfarin.
skin necrosis
*result in thrombotic occlusion of the microvasculature with skin necrosis.
warfarin-induced skin necrosis a rare complication that can occur in individuals with underlying ________ shortly after starting warfarin.
protein C or S deficiency
Many Caucasians have ____, which is modified to resist activated protein C. The resulting hypercoagulable state predisposes to deep vein thromboses
factor V Leiden
Many Caucasians have factor V Leiden which is modified to resist activated protein C. Consequences of the hypercoagulable state predisposes to ____ & ____
deep vein thromboses
&
PE
_____ is a plasma cell neoplasm associated with the overproduction of monoclonal immunoglobulins.
Multiple myeloma
Serum protein electrophoresis demonstrates a monoclonal spike in the gamma globulin region
and abnormal plasma cells. Diagnosis
Multiple myeloma
Multiple myeloma is treated with medications that block _____ activity (eg, bortezomib) or increase _______ of specific transcription factors like Lenalidomide.
proteasome
ubiquitination
Lenalidomide increases E3 ubiquitin ligase binding to transcription factors overexpressed causing increased transcription factor destruction by the proteosome and cancer cell death.
Give a pregnant women, _________ if she has thrombosis since it can’t cross placenta. pregnancy makes you hypercoagulable
LMW Heparin (Enoxaparin)
_______ rapidly reverses warfarin’s effects whereas vitamin K requires time for clotting factor re-synthesis.
Fresh frozen plasma
A normal bleeding time indicates adequate _______ function.
platelet hemostatic
A normal activated partial thromboplastin time (aPTT) indicates an intact ______ coagulation system.
intrinsic
Prolonged prothrombin time in the setting of normal aPTT indicates a defect in the extrinsic coagulation system at a step that is _______-.
not shared with the intrinsic system
aka Factor 7 deficiency
Factor XI deficiency results in a rare autosomal recessive disorder called ______.
Affected patients are at increased risk for bleeding following surgery or trauma.
prolonged aPTT
normal PT.
hemophilia C
How is desmopressin able to stop prolonged bleeding in Hemophilia A and Type-1 vWb Disease (2)
Increases circulating factor VIII
Increases endothelial secretion of vWF to stop bleeding
Hemophilia B must be treated with
factor 9 replacement
The thrombin time (TT) is prolonged with medications that directly or indirectly inhibit ______.
thrombin
________ inhibitors prolong both aPTT and PT with no effect on TT.
Direct factor Xa
_________ inhibitors directly inhibit platelet activity and have little overall effect on aPTT, PT, or TT.
Cyclooxygenase (Asprin)
_____ prevent the formation of thrombin (factor IIa), resulting in prolongation of aPTT, PT, and TT.
Direct thrombin inhibitors
dabigatran
Factor 2a is also known as
Factor 2 is aka
Thrombin
Prothrombin
_________ binds to antithrombin and causes inactivation of several coagulation factors, most significantly factor IIa (thrombin) and factor Xa.
aPTT and TT are prolonged
Unfractionated heparin
Unfractionated heparin binds to antithrombin and causes inactivation of several coagulation factors, most significantly _____ and ______.
factor IIa (thrombin) factor Xa
Patients with cystic fibrosis are at risk for fat-soluble vitamin (ie, A, D, E, K) deficiency due to fat malabsorption from pancreatic insufficiency which can cause a_____PT and ______aPTT
Vitamin K deficiency thus
prolonged PT
normal aPTT
Total body vitamin K does not contribute to a delay in warfarin efficacy.
However, increased intake of _______ can lead to subtherapeutic INR due to increased vitamin K availability in the liver.
foods rich in vitamin K (eg, green leafy vegetables)
Nephrotic syndrome is a hypercoagulable state which can cause renal vein thrombosis. Loss of _____, is responsible for the thrombotic complications
antithrombin III
_________- is a protein released from the alpha granules of platelets that plays a role in platelet aggregation. It also binds heparin and helps inactivate the molecule.
Platelet factor 4 (PF4)
Heparin-induced thrombocytopenia and thrombosis results from the production of IgG antibodies against _______.
The Fc component of these antibodies binds to platelets, resulting in widespread platelet activation (prothrombotic state) & splenic destruction of these platelets (Thrombocytopenia)
complexes of heparin and platelet factor 4.
