Principles hematology Flashcards
Three layers of the vessel wall
Intima: Inner, primarily endothelial cells
Media: middle subendothelial, contains collagen and bibronectin
Adventitia: outer, Controls blood flow by influencing the vessel’s degree of contraction
Procoagulants
Coagulation factors, collagen, vWF, protein C, protein S, fibronectin, thrombomodulin
Anticoagulant
antithrombin III
Vasodilation
nitric oxide
prostacyclin
vasoconstriction
thromboxane A2
ADP
serotonin
fibrinolytic
plasminogen
tPA
urokinase
antifibrinolytic
plasminogen activator inhibitor
Stages of vessel injury
The vessel wall immediately contracts to cause a tamponade, thereby decreasing blood flow
The area adjacent to the injury vasodilates and distributes blood to the surrounding organs and tissues
Contraction is followed by three separate stages in the formation of a primary plug:
1. adhesion (vWF)
2. activation
3. aggregation
What are the two separate pathways of the clotting cascade?
extrinsic and intrinsic
Extrinsic (tissue factor) pathway
Activated by release of tissue factor (TF) when damage occurs outside the vessel wall (i.e., organ trauma, crushing injury)
TF (factor III) activates proconvertin (factor VII) changing it to activated factor VII (VIIa)
Once activated, factor VII activates factor X (Stuart-Prower) of the common pathway
Factor X forms a complex with factor V (proaccelerin, a prothrombinase complex), activating factor II (prothrombin), which when activated becomes factor IIa (prothrombin)
Thrombin then activates factor I (fibrinogen) to form activated factor I (Ia, fibrin)
Clotting pathway
Intrinsic pathway (Contact activation pathway)
Initiated when damage occurs to the blood vessels themselves
Initiated by prekallikrein, high-molecular-weight kininogen (HMWK) , and by the activation of XII (Hageman)
With the help of calcium (factor IV), the coagulation pathways initiates a domino effect
Once activated, each factor activates its subsequent factor.
Factor XII activates factor XI, which activates factor IX, which then activates factor VIII, and ultimately merges at the common pathway and activates factor X. The result is the generation of fibrin from the activation of prothrombin to thrombin.
What factors does thrombin assist with?
activating factors V, VIII, I, and XIII
Influences platelet recruitment to the site of injury
Common Pathway
The terminal pathway of the coagulation cascade
Factor X has been activated by the extrinsic and intrinsic pathways
Factor X requires factor V (proaccelerin) and calcium to convert factor II (prothrombin) to its active-state thrombin (IIa)
Thrombin then activates factor I (fibrinogen)to its active form Ia (fibrin)
Factor XIII (fibrin-stabilizing factor) is required for the platelet plug to hold. It forms a cross-linked mesh within the platelet plug, increasing its strength.
Fibrin (factor Ia) and factor XIII secure a stable secondary plug and bleeding stops
Once a clot is made, it retracts, eliminating its serum
As the clot retracts, it weaves the edges of the vessel together, healing the injury
All the clotting factors and their names
What is fibrinolysis regulated by?
Fibrinolysis is regulated by plasma proteins
What does the Fibrinolytic System do?
Degrades fibrin once the hemostatic plug is no longer needed
Thrombin, which originally acted as a procoagulant, now acts as an anticoagulant and activates additional anticoagulant mediators
Which pathway do PT and aPTT go with?
PT - extrinsic
aPTT - intrinsic
normal PT 12-14 seconds
normal PTT 25-32 seconds
normal ACT 50-150
Platelet Infusion Guidelines
**Recommended dose: 1 plateletpheresis pack per 10 kg of body weight. This dose should increase the platelet count by 5,000 to 10,000 mm
Platelet transfusion even with a normal or absent platelet count if there is known or suspected platelet dysfunction
In surgical and obstetric patients, platelet transfusion is rarely indicated if platelet count is > 100,000 μL. Transfusion is indicated for platelet count < 50,000 μL
Normal lifespan: 7 to 10 days
Donated platelet lifespan: 4 to 5 days
Fresh Frozen Plasma Infusion Guidelines
*Contains all the clotting factors and naturally occurring inhibitors
Does not provide platelet replacement
Must be ABO compatible
Average FFP volume: 200 to 250 mL
Correction of excessive microvascular bleeding in the presence of an INR > 2.0 and the absence of heparin
Correction of excessive microvascular bleeding secondary to coagulation factor deficiency in patients transfused with more than one blood volume (approximately 70 mL/kg) and when PT/INR and an APTT cannot be obtained
Urgent reversal of warfarin therapy when prothrombin complex concentrate (PCC) is not available
Correction of a known coagulation factor deficiency for which specific concentrates are unavailable
FFP NOT indicated for:
PT/INR and APTT normal
Solely for increasing albumin level or plasma volume
Cryoprecipitate Infusion Guidelines
The precipitate collected off the top of FFP as it thaws
Rich in factors VIII, XIII, and fibronectin
Fibrinogen concentration < 80 to 100 mg/dL in the presence of bleeding
An adjunct in massively transfused patients where a fibrinogen level is not obtainable
Patients with congenital fibrinogen deficiencies
Rarely indicated if fibrinogen concentration is > 150 mg/dL
Transfusion Guidelines
Few fixed guidelines for transfusion
Guidelines vary by institution
Hgb < 7g/dL is recommended for high-risk patients
Alternatives to PRBC transfusion:
- Preoperative autologous donation
- Acute normovolemic hemodilution
- Blood cell salvage
- Recombinant factor VII
Used to treat hemophilia A (factor VIII) and B (factor IX), inhibitor disorders of factors VIII and IX, factor VII deficiency, and as a universal hemostatic agent
Use cautiously in patients with a history of thrombosis
How much does 1 unit of prbc’s (350ml) increase hemoglobin by?
by 1g/dL
How much does 1 unit of platelets (250 ml) increase platelets by?
30,000-60,000
Von Willebrand Disease (vWD):
Rare bleeding disorder
Can be inherited or acquired (secondary to cardiovascular, malignant, or immunologic diseases)
Von Willebrands treatment options
Desmopressin, high-dose IV immunoglobulins, FVIII/vWF concentrates, plasma exchange
Type 1: desmopressin
Type 2 and 3: require vWF concentrate administration
Tranexamic acid is also an important adjunctive therapy as either
Hemophilia A is a Factor _____ deficiency
Hemophilia B is a Factor _____ deficiency
Hemophilia A: Factor VIII deficiency
Hemophilia B: Factor IX deficiency
Hemophilia symptoms
Spontaneous bleeding
Muscle hematomas
Joint pain
Treatment for hemophilia
Desmopressin
Factor VII
Perioperative Management of the Hemophilic Patient:
Preoperative assessment of inhibitor screening and inhibitor assay completed within 1 week of surgery
Elective procedures early in the day
Desmopressin is ok for hemophilia A but of no use in hemophilia B because it does not affect factor 9. Cryo preferred over ffp for A
Treatment with viral inactivated plasma-derived or recombinent concentrates is preferred over cryo or ffp.
Disseminated Intravascular Coagulation (DIC):
A result of intravascular coagulation activation with microvascular thrombi formation, which causes thrombocytopenia and clotting factors depletion, leading to bleeding and end-organ complications
Systemic coagulation activation results in intravascular fibrin deposits, thrombotic microangiography, compromised blood supply to organs, and multiorgan system failure
DIC diagnosis
Laboratory tests: platelet count, aPTT, PT, fibrin-related markers (fibrin degradation products, D-dimer), fibrinogen, and antithrombin
International Society of Thrombosis and Hemostasis (ISTH) developed a DIC scoring system (score > 5 overt DIC, < 5 suggestive but not affitmative of nonovert DIC)
Treatment of DIC
Depends on the underlying condition
Identify and eliminate the underlying cause
No treatment if mild, asymptomatic, and self-limited
Obstetrics: DIC many resolve with prompt delivery of the fetus
Sepsis: antibiotics
Platelets, FFP, cryoprecipitate
Antithrombotics are controversial
Sickle Cell Disease
Common, hereditary hemoglobinopathy
An autosomal recessive genetic abnormality of the β-globin that codes for production of variant hemoglobin, hemoglobin S
Hemoglobin SS
Hemoglobin SC
Hemoglobin SB- (Beta) thalassemia
Beta-zero thalassemia
Sickle Cell Disease: Intraoperative Management
Adequate hydration
avoid hypoxemia
maintain normothermia
they have LOTS OF PAIN
caution using vasoocclusive devices like tournaquets
for patients with pulmonary disease, maybe decrease hemoglobin S level to below 30%
Heparin-Induced Thrombocytopenia (HIT):
An immune response to heparin that can progress to severe thrombosis, amputation, and death
Suspect HIT when a patient receiving heparin experiences a 50%+ drop in platelet count
Clinical presentation of HIT
thrombocytopenia, resistance to heparin anticoagulation, thrombosis, and positive assay tests indicative of HIT
Gold standard DIAGNOSIS OF hit
C-serotonin release assay
Treatment of HITBased on clinical presentation and laboratory findings
Stop heparin immediately
Administer direct thrombin inhibitors (argatroban or lepirudin)
Prompt surgical intervention for thrombosis that compromises peripheral perfusion
Type 1 HIT vs Type 2 HIT
Type I:
Thrombocytopenia is mediated by direct heparin-induced platelet
aggregation (e.g., nonimmune mediated)
* Onset is typically 1 to 4 days after start of heparin therapy
* Mild thrombocytopenia (e.g., less than 100,000 per microliter)
* Thrombocytopenia often resolves spontaneously even with
continued administration of heparin
* Typically occurs with high-dose heparin administration
* Not associated with thrombosis and serious clinical sequelae
Type 1 HIT vs Type 2 HIT
Type II:
* Thrombocytopenia is mediated by the actions of the heparin,
platelet factor 4, and immunoglobulin G expression (e.g.,
immune mediated)
* Onset is typically 5 to 14 days after start of heparin therapy
* Severe thrombocytopenia (e.g., less than 60,000 per microliter)
* Thrombocytopenia does not resolve spontaneously, therefore
heparin administration must be discontinued
* Occurs with any heparin dose and route
* Associated with thrombosis and serious clinical sequelae
Differences type 1 and type 2 HIT
Type 2 takes longer to develop, is worse, is immune mediated, severe thrombocytopenia, and occur with any dose or route
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Additional Risk Factors for Acute coronary Stent Thrombosis
Site of stent placement (e.g., bifurcation stenting, side branch occlusion)
Left main coronary artery stent
Long stent length (greater than 18 mm)
Ostial stenting
Overlapping stents
Placement of multiple stents
Small stent diameter (less than 3 mm)
Suboptimal stent placement
Patient risk factors for coronary stents
Patient Risk Factors:
Advanced age
Diabetes mellitus
Gene polymorphism
Hypercoagulable states (e.g., diabetes, malignancy, and surgery)
Major cardiac adverse event within 30 days of percutaneous cardiac intervention
Reduced left ventricular ejection fraction
Prior brachytherapy
Renal insufficiency
Elective noncardiac surgery should be delayed ___ days after bare metal stent placement and ___ months after drug eluting stent placement
Elective noncardiac surgery should be delayed 30 days after bare metal stent placement and 6 months after drug eluting stent placement
