Hematology Learning Journal - Week 8 Objectives

Hemostasis

Process to stop blood flow

Goals of Hemostasis

Maintain blood flow, form a barrier, limit the barrier, dissolve the clot

Elements of Hemostasis

Vasculature, platelets, plasma proteins

Primary Hemostasis

Forms platelet plug, induces fibrin clot formation

Secondary Hemostasis

Forms fibrin-reinforced plug, stops bleeding

Fibrinolysis

Breakdown clot, prevents excess clotting

Hemophilia

Excessive bleeding, malfunction in primary or secondary hemostasis

Thrombophilia

Excessive clotting, malfunction in fibrinolysis

Quality Assurance Components

SOPs, specimen ID, error documentation, maintenance logs, phlebotomy issues

Accuracy

Exactness compared to true value

Precision

Closeness of measurements to each other

Reliability

Ability to maintain precision and accuracy

Delta Check

Comparing current and previous results for change identification

Diagnostic Sensitivity

Proportion of diseased patients with positive test

Diagnostic Specificity

Proportion of non-diseased patients with negative test

Systematic Error

Errors in test system or method

Random Error

Unpredictable mistakes

Shift

Sudden change in values

Trend

Gradual shift in values over multiple measurements

Westgard Rules

Control value guidelines for lab QC

External QC

Assess lab accuracy, required by accrediting agencies

Platelet Regions

Peripheral, structural, organelle, membrane systems

Glycocalyx Function

Rich in glycoproteins, contributes to negative charge

Platelet Receptors

Glycoprotein Ib/IX, IIB/IIIa, Va for various factors

Structural Zone Role

Support, shape change responsibility

Granule Contents

Alpha: protein factors, Dense: non-protein factors

OCS & DTS Functions

Communication, calcium regulation

Platelet Adhesion

Via glycoprotein Ib/IX to vWF and collagen

Platelet Agonists

Collagen, fibronectin, vWF, thrombin, ADP

Factor XIIa Functions

Cleaves prekallikrein, XI, and plasminogen

Factor VIII Function

Aids X activation by IXa, circulates with vWF, activated by thrombin

Factor VIII Inhibitor

Protein C inactivates Factor VIII

vWF Circulation Form

vWF circulates as polymers

Factor II Activation Factors

Calcium, Va, and Xa activate Factor II

Factor II Functions

Converts fibrinogen to fibrin, activates FXIII, platelet aggregation, and other factors

Fibrin Clot Formation Steps

Proteolytic cleavage, spontaneous polymerization, stabilization by FXIIIa

Fibrinogen Concentration

Fibrinogen has the highest blood concentration

Fibrin Monomers Crosslinking

XII activated by thrombin with Ca and fibrinogen, XIIIa cross-links antiplasmin to fibrin

Vitamin K-Dependent Factors

Include II, VII, IX, X, Protein C, and Protein S

Coumarin Anticoagulants

Inhibit vitamin K reduction, monitored by PT test

ATIII Function with Heparin

ATIII forms inactive complexes with proteases, heparin increases reaction rate

Heparin Inactivation

Specifically degraded by heparinase, used to confirm prolonged PTT due to heparin

Protein C and Protein S Functions

Protein C inactivates VIIIa and Va, Protein S is a cofactor for Protein C

Coagulation Sample Tube

Light blue sodium citrate tube for coagulation tests

PT Test Components

Evaluates extrinsic pathway with tissue factor, calcium; INR used for Coumarin therapy

INR Target Ranges

Ranges for A-fib, mechanical heart valves, and panic value

APTT Test Components

Evaluates intrinsic pathway with various factors, monitors heparin therapy

TT Test Components

Evaluates fibrinogen deficiency, reptilase-R test for specific fibrinogen deficiency

Anti-Xa Assay

Monitors heparin concentration, measures Xa inhibition

Direct Thrombin Inhibitors

Bind thrombin independently of ATIII, used in heparin-intolerant patients

Factor Deficiency Scenarios

Identifies factor deficiencies based on PT and APTT results

Mixing Study Interpretation

Differentiates factor deficiencies based on PT and APTT responses

Diagnosing Factor Deficiencies

Approach using PT/APTT, mixing study, and factor assay

Plasminogen Activation

Activated by tissue plasminogen activator, XIIa, kallikrein, and HMWK

D-Dimer Test Significance

Specific for FDP, indicates clot formation and lysis

TEG Report Parameters

Defines R, K, alpha, MA, A30 and their clinical implications

Vascular System Components

Arteries, veins, capillaries, and their hemostatic functions

Microangiopathic hemolytic anemia

Anemia due to platelet clotting in small blood vessels

Thrombocytopenia

Low platelet count

Neurologic symptoms

Symptoms like headaches and seizures

Fever

Elevated body temperature

Renal disease

Kidney-related illness

Platelet aggregating factor

Thromboxane production

Platelet aggregating inhibitor

Prostacyclin deficiency

Immature platelets

Increased mean platelet volume

Bone marrow platelet production

Increased production of platelets in the bone marrow

Marrow megakaryocytes

Increased presence of large bone marrow cells

BT (Bleeding Time)

Time taken for bleeding to stop

Acute ITP

Sudden onset, platelet count <20 x 10^3 /uL, self-limited

Chronic ITP

Slow onset, platelet count 30-80 x 10^3 /uL, associated with SLE

HIT

Heparin-induced thrombocytopenia

Pseudothrombocytopenia

Platelet clumping due to EDTA exposure

Essential thrombocytosis causes

Clonal proliferation of hemopoietic cells

Secondary thrombocytosis disorders

Result from iron-deficiency anemia, chronic inflammatory disease

Glanzmann's Thrombasthenia

Defective platelet aggregation, IIb or IIIa glycoproteins affected

Bernard-Soulier Syndrome

Dec in vWF, normal receptor, giant platelets

Dense granule deficiencies

Seen in Hermansky-Pudlak, Chediak-Higashi, Wiskott-Aldrich syndromes

Chediak-Higashi clinical presentations

Lysosome dysfunction, reduced pigment, platelet dysfunction

Neutrophil morphology in CHS

Large slate blue granules

Grey platelet syndrome

Alpha granule deficiency, diminished aggregation and release properties

Acquired platelet function disorders

Result from cardiopulmonary bypass, SLE, kidney failure, and certain syndromes

Hereditary fibrinogen disorders

Include afibrinogenemia, dysfibrinogenemia, FXIII deficiency

DIC pathophysiology

Fatal, consumption coagulopathy, increased FDPs, decreased platelets and fibrinogen

DIC causes

Extrinsic and intrinsic system activation leading to coagulation pathway hyperactivation

Primary fibrinogenolysis

Inc plasmin levels without clot formation, prolonged clot dissolution

Liver disease impact on coagulation

Decreased factor VII, increased PT, APTT, TT

Reptilase time test

Sensitive to heparin overdose detection

Hemophilia A presentations

Factor VIII deficiency, severe to mild based on activity levels

Hemophilia A treatments

Factor VIII replacement therapy, cryoprecipitate, DDAVP

Hemophilia B presentations

Factor IX deficiency, similar symptoms to hemophilia A

Hemophilia B treatments

FFP, less frequent treatment than hemophilia A

VWD pathophysiology

Deficiency in vWF, skin/mucosa hemorrhage common

VWD lab findings

Prolonged BT, aPTT, normal PT, impaired platelet aggregation

Prekallikrein deficiency APTT test

Prolonged incubation normalizes APTT

Hemophilia B

Deficiency of factor IX due to gene mutation

Sex-linked

Genetic trait carried on the sex chromosomes

Lab Findings Hemophilia B

Prolonged APTT, normal BT, PT, TT

Treatment Hemophilia B

FFP preferred, less frequent than hemophilia A

VWD

Deficiency in vWF causing bleeding

Lab Findings VWD

Prolonged aPTT, BT; normal PT; impaired platelet aggregation