20 - Introduction to Coagulation Disorders & Acquired Disorders Flashcards
Coagulation Pathway
Coagulation Pathway
Coagulation Pathway
Coagulation Pathway
Coagulation Pathway
Evaluation of the bleeding patient
- Type of bleeding:
- Local versus diffuse
- Spontaneous or secondary to trauma
- Excessive or minimal
- Mucosal or deep tissues /joints
- Bruising/petechial
- Early or late
- History:
- Personal history of bleeding
- Family history of bleeding
- Medical conditions or recent trauma (surgery is a form of trauma)
- Medications: prescribed and OTC, vitamins and herbs
- Nutritional status
Types of bleeding:
Localized or diffuse
Evaluation of the bleeding patient
Labs
- Platelet count
- PT INR
- PTT
- Liver function studies
- Renal function studies
- Fibrinogen
- Thrombin Time
- Platelet function
- Peripheral smear
Evaluation of the bleeding patient
Labs: PT INR and aPTT
PT INR
(prothrombin time)
- measures how long it takes for a
clot to form in a blood sample. - An INR (international normalized
ratio) is a type of calculation
based on PT test results. - in order to activate the extrinsic
pathway, tissue factor (factor III)
is added and the time the sample
takes to clot is measured
optically. - A normal PT requires factors I
(fibrinogen), II (prothrombin), V
(proaccelerin), VII (proconvertin),
and X (Stuart-Prower factor).
aPTT
(activated partial thromboplastin time)
* measures how long it takes for a
clot to form in a blood sample.
* In order to activate the intrinsic
pathway an activator (such as
silica, celite, laolin, or ellagic acid)
is added, and the time the sample
takes to clot is measured optically.
* A normal PTT requires factors I, II,
V, VIII, IX, X, XI and XII. Notably,
deficiencies in factors VII or XIII will
not be detected with the PTT test.
Coagulation pathways
Common Acquired Bleeding Disorders
Case 1:
* A 27-year-old pediatric resident comes to your ER feeling terrible. He has had a “cold” with high fever for the past few days. His only significant past medical history was that he received radiation for Hodgkin’s disease at the age of 16. He has been well without evidence
of recurrence since then.
- His physical exam was remarkable for: a temperature of 104F, P 175, R 28, BP 70/50. He had rales in his left anterior chest, a well healed midline abdominal scar, and diffuse petechiae and ecchymoses covering a large portion of his body (which his wife said were not
present earlier in the day).
LABS:
▪ WBC 3,500/ul
▪ ANC 700/ul !
▪ ALC 2,800/ul
▪ Hemoglobin 14.0 gm/dl
▪ Hematocrit 42%
▪ Platelets 6,000/ul !
▪ PT 16 sec, INR 2 !
▪ aPTT 58 sec !
Disseminated Intravascular Coagulation
▪ Increased activation of the clotting cascade
▪ Decreased natural anticoagulants
▪ Impaired fibrinolysis
Conditions associated with DIC
Clinical manifestations of DIC: Thrombotic
- Brain - Altered mental status, Stroke
- Renal - Acute renal failure
- GI - Mucosal ulceration, bleeding
- Skin - Digital ischemia, Purpura fulminans
- Lungs - ARDS
- Adrenals:
Waterhouse-Friderichsen syndrome
Acute adrenal infarction or hemorrhage
Adrenal insufficiency
Clinical Manifestation of DIC: Hemorrhagic
- Global bleeding
- Consumptive
thrombocytopenia - Consumption of coagulation
factors - Fibrinogen, FVIII, etc.
- FDPs inhibit fibrin
polymerization and thus
hinders platelet aggregation
Clinical Manifestations of DIC: Thrombotic
Diagnosis of DIC
▪ Prolonged PT INR
▪ Prolonged pTT
▪ Thrombocytopenia
▪ Decreased fibrinogen (sometimes NML; acute
phase reactant)
▪ Schistocytes on peripheral smear
▪ Decreased ATIII, protein C, protein S
▪ Increased FDP/FSP (fibrin split products), D-Dimer
Case 2: An 18-year-old man is admitted to the Trauma Unit for abdominal gunshot wounds. He requires
multiple surgeries for bowel resection and draining
abscesses. He is NPO and has been getting broad
spectrum antibiotics for the past 3 weeks. Hematology
is consulted for a prolonged PT and PTT.
Vitamin K deficiency
Vitamin K Function
- Factors II, VII, IX, X have 10 - 13
glutamic acid residues - Vitamin K necessary cofactor for
g-carboxylation of glutamic acids
[g-carboxyglutamic acid (gCGA)] - Factor activity is proportional to
the number of carboxylated
glutamic acids on the molecule - Ca2+ acts as a bridge between g-
carboxyglutamic acid and
negatively charged platelet
phospholipids
coagulation pathway
End stage liver disease: thrombosis
- Increased vWF/FVIII
- Decreased ATIII
- Decreased protein C and protein S
- Decreased plasminogen
- Decreased ADAMTS13
Differentiating between Vitamin K deficiency, Liver disease, and DIC
Case 4
A 65-year-old man has progressive bruising after hitting a wall moving furniture. Hecomes to the ER for a painful, swollen left leg. He has no bleeding history.
Labs:
Platelets 355,000
PT 10.6
PTT >100
TT 18.2
Fibrinogen 347
PTT mixing study
Control 32 s
Mix at 2 hours, 98 s
Factor VIII <1%
Factor IX 70%
Factor XI 105%
Factor XII 108%
End Stage Renal Disease
▪ The primary effect is on decreasing platelet function. Platelet dysfunction occurs both as a result of intrinsic platelet abnormalities and impaired platelet-vessel wall interaction.
▪ If a patient with ESRD has platelet type bleeding, no matter what the platelet count, a platelet transfusion can be considered.
▪ DDAVP (vasopressin) as a single dose can be considered as it will cause immediate activation of V2 vasopressin receptors on endothelial cells and intracellular cyclic adenosine monophosphate (cAMP)–dependent signaling leading to exocytosis of von Willebrand factor (VWF) and tissue plasminogen activator from Weibel-Palade bodies as well enhancing intracellular Na+ and Ca2+ fluxes. This all serves to activate the platelets.
