MLAB 1227: Coagulation
Keri Brophy-Martinez
Coagulation Disorders:
Secondary Hemostasis
Part Two
Acquired Coagulation Disorders
Two or more factors generally affected, more
complicated
 Bleeding from multiple sites
 More common than hereditary disorders
 Classification

1.
2.
3.
4.
5.
DIC
Primary Fibrinogenolysis
Liver Disease
Vitamin K Deficiency
Acquired Pathologic Inhibitors
1. DIC: Disseminated Intravascular
Coagulation

Consumption 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: 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 DIC
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?

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?

Step 3: Uncontrolled plasmin and
thrombin enter circulation
◦ Why?
 Inhibitors such as AT have been depleted
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 DIC

Platelet count: decreased
◦ (40-75 x 109/L)
PT: increased
 PTT : increased
 Fibrinogen: decreased
 FDP /D-dimer: positive

◦ **Most helpful in diagnosis
AT : decreased
 RBC fragments: present

DIC

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 Fibrinogenolysis
Similar to DIC
 Plasminogen is inappropriately activated
to plasmin
 Plasmin circulates overwhelming the
antiplasmin inhibitors and degrading
fibrinogen and factors V,VIII, XIII
 No thrombin is generated
 Liver disease is a common trigger

3. Liver Disease
Affects 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 Deficiency
Liver 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 Inhibitors
Develop 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 Inhibitors
1.
◦
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 Inhibitors
Lupus Inhibitor/Anticoagulant
2.
◦
◦
◦
◦
◦
Seen in patients with autoimmune diseases, drug
reactions, but also in normal patients
Autoantibodies interfere with phospholipiddependent 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 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
Macrocytes
Targets,
acanthocytes
Normal
Normal
Normal
References

McKenzie, Shirlyn B., and J. Lynne.
Williams. "Chapter 32." Clinical
Laboratory Hematology. Boston:
Pearson, 2010. Print.