MLAB 1227: CoagulationMLAB 1227: CoagulationKeri Brophy-MartinezKeri Brophy-Martinez

Coagulation Disorders: Secondary HemostasisPart Two

Acquired Coagulation Acquired Coagulation DisordersDisordersTwo or more factors generally

affected, more complicatedBleeding from multiple sitesMore common than hereditary

disordersClassification

1. DIC2. Primary Fibrinogenolysis3. Liver Disease4. Vitamin K Deficiency5. Acquired Pathologic Inhibitors

1. DIC: Disseminated 1. DIC: Disseminated Intravascular CoagulationIntravascular CoagulationConsumption Coagulopathy

◦ As fibrin is formed, clotting proteins and naturally occurring inhibitors and platelets are consumed faster than they are made

◦ Thrombo-hemorrhagic disorder Clotting and lysing occurring in blood vessel, at

the same time◦ Life threatening◦ Bleeding is the most apparent

characteristic◦ Initiating events are thrombotic, where

material enters circulation ◦ Occurs due to lack of the negative

feedback mechanism◦ Affects young and elderly

DIC: TriggersDIC: Triggers Obstetric – usually due to major tissue damage such as

retained dead fetus, abruptio placentae, or placenta previa

Acute leukemias – Promyelocytic – increase number of granules released into circulation as cells break down

Intravascular hemolysis – ex: transfusion reaction Massive trauma (especially crushing injuries), burns,

surgical procedures Heat stroke Snake venoms Septicemias and infections – viral, bacterial, rickettsial,

fungal, protozoan (especially gram negative that release endotoxins)

Tumors – foreign tissues and cells Prosthetic devices – heart valves, aortic balloon,

peritoneal shunting Vascular disease – damaged endothelial lining

Course of DICCourse of DIC

DIC: How Does It Occur?DIC: How Does It Occur?

Step 1: Out of control clotting◦Causes widespread fibrin

deposits in vessels of tissues and organs

◦Subsequent event: Hemorrhage Clotting proteins consumed at a high

rate Causes multiple factor deficiencies,

especially fibrinogen group

Platelets caught in thrombi and removed

DIC: How Does It Occur?DIC: How Does It Occur?

Step 2: Triggers Fibrinolytic system to remove fibrin◦Results in:

Circulating degradation products (FDPs) that interfere with platelet function & normal clot formation

Degradation of Factor V & VIII

DIC: How Does It Occur?DIC: How Does It Occur?

Step 3: Uncontrolled plasmin and thrombin enter circulation◦Why?

Inhibitors such as AT have been depleted

DIC: How Does It Occur?DIC: How Does It Occur?

Step 4: Appearance of Symptoms◦Bleeding from multiple sites◦Petechiae◦Purpura◦Occlusions in organs◦Oozing from needle puncture

sites◦Shock

Lab Features of DICLab Features of DIC

Platelet count: decreased ◦(40-75 x 109/L)

PT: increasedPTT : increasedFibrinogen: decreased FDP /D-dimer: positive

◦**Most helpful in diagnosisAT : decreasedRBC fragments: present

DICDIC

Treatment◦Goal is to treat the underlying

condition Remove the triggering process –

treat with antibiotics, antineoplasms, remove dead tissue, treat the diseases or conditions

◦Heparin – to prevent or limit further coagulation

◦Replace factors, platelets = give FFP

2. Primary 2. Primary FibrinogenolysisFibrinogenolysisSimilar to DICPlasminogen is inappropriately

activated to plasminPlasmin circulates overwhelming

the antiplasmin inhibitors and degrading fibrinogen and factors V,VIII, XIII

No thrombin is generatedLiver disease is a common trigger

3. Liver Disease3. Liver DiseaseAffects all proteins made in the

liver that function in fibrin formation, fibrinolysis and inhibition.

Patients show minimal bleeding, except in severe cases

Lab features◦Increased

PT,PTT◦Decreased

Platelets

4. Vitamin K Deficiency4. Vitamin K DeficiencyLiver cells able to make precursor

protein but the calcium binding site is nonfunctional

Causes◦Malabsorptive syndromes

Sprue Obstruction in biliary tract Ingestion of vitamin K inhibitors- like warfarin

◦Antibiotic therapy Kills off normal flora in gut which made

vitamin K

5. Acquired Pathologic 5. Acquired Pathologic InhibitorsInhibitorsDevelop in patients with certain

disease states and others with no underlying conditions

Circulating anticoagulants which may develop against any clotting factor

Classed as immunoglobulins◦Either IgG or IgM◦Can be alloantibodies or autoantibodies

Types of InhibitorsTypes of Inhibitors1. Directed towards a single

coagulation factor◦ Seen in patients with inherited factor

deficiencies that have had replacement therapy for bleeding complications

◦ Less commonly seen in healthy people and those taking certain drugs

◦ Rare, except Factor VIII & IX◦ How do we find them?

Interfere with clotting factor activity PTT prolonged, other tests normal Mixing study: test will still be prolonged

Types of InhibitorsTypes of Inhibitors2. Lupus Inhibitor/Anticoagulant

◦ Seen in patients with autoimmune diseases, drug reactions, but also in normal patients

◦ Autoantibodies interfere with phospholipid-dependent reagents used in PTT tests

◦ Patients have no bleeding problems (though some have an increase risk of thrombosis)

◦ In vitro, any coag test using a phospholipid reagent will be falsely prolonged (PT, PTT)

◦ Coag studies must be performed using reagents that do not contain phospholipids

Comparison of Acquired DisordersComparison of Acquired Disorders

Test DIC Primary Fibrinogenolysis

Severe Liver Disease

Vitamin K Deficiency

Factor Inhibitor

Lupus Anticoagulant

Platelet Count

Dec Normal Dec Normal Normal Normal

PT Inc Inc Inc Inc Normal, except VII inhibitor

Normal

APTT Inc Inc Inc Inc Inc Inc

Fibrinogen

Dec Dec Dec Normal Normal Normal

D-dimer Inc Normal Normal Normal Normal Normal

Plasminogen

Dec Dec Normal-dec Normal Normal Normal

Antithrombin

Dec Normal Dec Normal Normal Normal

Blood Smear

Fragments

Normal MacrocytesTargets, acanthocytes

Normal Normal Normal

ReferencesReferences

McKenzie, Shirlyn B., and J. Lynne. Williams. "Chapter 32." Clinical Laboratory Hematology. Boston: Pearson, 2010. Print.