Objective 10

What is DIC (Disseminated Intravascular Coagulation)?

• common cause of destructive thrombocytopenia

• PLTs are consumed

• consumptive coagulopathy that entraps PLTS in an intravascular clots

• fibrin microthrombi can partially occlude small vessels and consume PLTS, coagulation factors, regulatory proteins, and fibrinolytic enzymes

What is the key feature of DIC?

• consumption coagulopathy

What are Quantitative PLT disorders?

involve abnormal platelet counts (usually thrombocytopenia) due to:

• Decreased production

• Increased destruction

• Consumption

• Sequestration

Describe the Etiology of DIC.

• Systemic activation of coagulation → widespread fibrin clot formation

• Leads to:

  • Consumption of platelets + clotting factors

  • Secondary fibrinolysis

Describe the pathophysiology of DIC

• accumulation of thrombin → release of TF → soluble fibrin monomers fail to polymerize and will coat PLTS and coagulation proteins

• plasmin will digest fibrin and fibrinogen

• PLTs are activated by thrombin and drive coagulation

• regulatory proteins are neutralized by soluble fibrin monomer

What are the main triggers of DIC?

• endotoxins

• venom

• hemangioma

• acute promyelocytic leukemia

• abruptio placentae

• massive trauma burns

What can cause DIC?

• Sepsis (most common)

• Trauma

• Malignancy

• Obstetric complications

What results will indicate Acute DIC?

• Increased

  • PT, APTT, TT, RT, D-dimer

• Decreased

  • fibrinogen and PLT count

What results will indicate Chronic DIC?

• PT, APTT, TT, fibrinogen, and PLT count are normal or mildly abnormal

What is acute DIC?

• decompensated state

• active hemorrhage is evident and consumption of coagulation factors and PLTs exceeds capacity to increase synthesis of these components

What is chronic DIC?

• compensated state

• rate of synthesis of coagulation components is balanced with rate of destruction

What will a peripheral blood smear show for someone with DIC?

• schistocytes form due to shearing of RBC by fibrin strands

What clinical presentations are associated with DIC?

• BOTH:

  • Bleeding (petechiae, oozing, hemorrhage)

  • Thrombosis (organ failure, ischemia)

• Can progress to multi-organ failure

What other lab findings will indicate DIC?

• Soluble fibrin monomer: +

• protein C and protein S: decreased

• Plasminogen: decreased

• Prothrombin fragment 1 and 2: increased

• factor assay: decreased

What DIC score will indicate DIC is present?

• any number > 5

What treatment for DIC will help slow the clotting process?

• UFH (Unfractionated Heparin)

What treatment for DIC will help replace missing PLTS and coagulation factors?

• FFP

• PCC

• Cryo

• Factor VIII

• RBC

• PLTs

What is Acute ITP (Immune Thrombocytopenic Purpura)

• affects children

• has abrupt bleeding manifestations (bruising, petechiae, epistaxis)

• thrombocytopenia

• follows a viral infection

What is Chronic ITP?

• affects females more than males

• insidious onset

• bleeding manifestations: mucocutaneous, menorrhagia, epistaxis, petechiae

• does NOT follow and infection

What is the etiology of chronic ITP?

• IgG antibody directed against PLT receptors

  • GPIIb/IIIa

  • GPIb

  • shortened lifespan

Describe the pathophysiology of Chronic ITP?

• antibody (IgG) directed against PLTs → thrombocytopenia

What is the main clinical finding of ITP?

• petechiae

What will a peripheral blood smear show with someone who has ITP?

• large PLTs

• lymphocytes

• segmented neutrophils

What medications is used for ITP?

• Prednisone

• IVIG

• Rituximab

• Win-Rho

What treatments are used for ITP?

• splenectomy

• antifibrinolytic agents

• Eltrombogap/Avatrombopag

What lab findings indicate ITP?

• ↓ Platelets ONLY

• Normal PT, aPTT

• Large platelets (↑ megakaryocytes in marrow)

What is TTP (Thrombotic Thrombocytopenic Purpura)

• characterized by triad of MAHA, thrombocytopenia, and neurologic abnormalities

• linked to viral illness and deficiency of ADAMTS13

What is the etiology of TTP?

• Deficiency of ADAMTS13 enzyme

• Leads to accumulation of large vWF multimers

• Causes platelet aggregation + microthrombi

What neurologic abnormalities will present with TTP?

• headache

• parestesia

• coma

What clinical presentations will occur with TTP?

• Thrombocytopenia

• Microangiopathic hemolytic anemia (MAHA)

• Neurologic symptoms (confusion, stroke)

• Fever

• Renal dysfunction (mild)

What will appear on a peripheral blood smear with someone who has TTP?

• schistocytes

• microspherocytes

• polychromasia

• NRBCs

• Low PLTs

What lab findings will indicate TTP?

• decreased haptoglobin

• hemoglobinemia/hemoglobinuria

• PT, APTT, fibrinogen, and D-dimer normal

• decreased ADAMTS13

What is polychromasia?

• immature RBC that appear blue (visualized with Wrights stain)

• if a blue smear was stained with new methylene blue, RBC would be identified as reticulocytes

What treatment is used for TTP?

• Plasma exchange

  • removes large multimers and supplies ADAMTS13

• Cryo-poor plasma

  • lacks fibrinogen, vWF, FVIII, and FXIII

What is HUS (Hemolytic Uremic Syndrome)?

• Endothelial damage → platelet activation → microthrombi

• self limiting and predominantly effects children

What causes 90% of HUS cases?

• Shigella Toxin Producing E.coli (O157:H7)

What clinical findings are associated with HUS?

• Renal Failure

• Thrombocytopenia

• MAHA

• common in children

What lab results are associated with HUS?

• Thrombocytopenia

• Renal failure

  • elevated BUN, creatine, hematuria and proteinuria

• Hemolytic anemia

  • elevated reticulocytes, schistocytes

  • HBG< 10 g/dl

What is Atypical HUS?

• caused by uncontrolled activation of complement system

• blood clots occur in kidney/ block blood flow

• tissues are attacked by complement

• linked to mutations that affect factor H, C3,B, and I

What is used to treat Atypical HUS?

• Eculizumab

What is used to treat HUS?

• eculizumab and eculizumab (atypical HUS)

• supportive therapy: STEC- HUS

What is HELLP (Hemolysis, Elevated Liver Enzymes, Low PLTS)

• condition seen in pregnancies with severe preeclampsia

• PLTs are activated in mother and fibrin deposits in the liver

What is used to treat HELLP?

• delivery of fetus and placenta ASAP

What is the Etiology of HELLP?

• Severe form of preeclampsia

• Endothelial dysfunction → platelet activation + hemolysis

What is HELLP linked to?

• Pre-eclampsia - hypertension, increased uric acid, thrombocytopenia

• Eclampsia - more severe with senziers and renal dysfunction

Describe the pathophysiology of HELLP.

• microvascular endothelial damage and intravascular PLT activation = PLT aggregation and tissue damage

What is seen on a peripheral blood smear with someone who has HELLP?

• spherocytes

• shistocytes

• burr cells

What clinical presentations are common in HELLP?

• Pregnant (3rd trimester)

• RUQ pain

• Nausea/vomiting

• Hypertension

What lab findings indicate HELLP?

• decreased PLT count

• increased liver enzymes

• increased LDH

• decreased hemoglobin/ hematocrit

• schistocytes, spherocytes, and burr cells

What are the main lab findings of HELLP?

• ↓ Platelets

• ↑ AST/ALT

• ↑ LDH

• Hemolysis (schistocytes)

What other treatment is used for HELLP?

• Corticosteroids to improve fetal lung maturity

• aspirin to treat preeclampsia

What are the PLT count parameters for the DIC score?

>100,000/ul = 0

<100,000/ul = 1

<50,000/ul = 2

What are the PT parameters for the DIC score?

< 3 sec prolonged = 0

>3 to 6 seconds prolonged = 1

> 6 sec prolonged = 2

What are the fibrinogen parameters for the DIC score?

>100 mg/dl = 0

<100 mg/dl = 1

What are the d-dimer parameters for DIC score?

no increase = 0

moderate increase = 2 (250-5000)

strong increase = 3 (>5000)