Coagulation Disorders 1 (CMPP)

What are signs of primary hemostasis disorders

Epistaxis

Mucosal Bleeds

GI Bleeds

Superficial ecchymosis

Petechiae

Dry Purpura

Wet Purpura

Wet Purpura

Blood filled blisters that are the sign of severe thrombocytopenia

What are signs of secondary hemostasis issues

Hemarthrosis

IM Bleeding

Spontaneous hematomas

Large-vessel bleeding

What is part of the acute workup for coagulation disoreders

CBC

PT/INR

aPTT

Fibrinogen

Peripheral Smear

Consider: PFA-100 + VWD testing

What is part of the chronic workup for coagulation disorders

CBC

PT/ INR

aPTT

If mucocutaneous bleed is noted: PFA-100 and VWD test

What are levels of concerns of thrombocytopenia

< 50k = Risk of Surgical Bleed

30-150k = May be asymptomatic with minor traumas

< 20k = Risk of Severe Spontaneous Bleed

What are concerned thrombocytopenic emergency

PTL < 50k w/ active bleed, uregent invasive procedure, or pregnant

Suspected HIT

Suspected TTP

HUS

Suspected acute leukemia

Suspected aplastic anemia / bone marrow failure syndromes

Pseudothrombocytopenia

A false decrease in the PTL count due to PTL clumping looking like WBC

What is the work-up for asymptomatic thrombocytopenia?

Repeat the CBC with a smear

Look for alternate causes

When should a repeat CBC for thrombocytopenia in an asymptomatic patient be done

PTL > 50-100k in 1-2 weeks

PTL > 100-149k in 1-2 months

What are some causes of asymptomatic thrombocytopenia

HIV

Hep C / Chronic Liver Disease

ITP

Parvovirus

EBV

Medications

What medications can induce thrombocytopenia

Quinine

Acetaminophen

Naprosyn

Valacyclovir

Valproic Acid

Sulfamethoxazole

Daptomycin

Linezolid

Idiopathic Thrombocytopenic Purpura (ITP)

Condition of acquired autoimmunity to PTLs

What is the Ag and Ab in ITP

IgG against GPIIb/IIIa

What are some inciting events for ITP

HIV

Hep C

CMV

Varicella

Antiphospholipid Syndrome (APS)

SLE

How does ITP present

Insidious Onset and Often Asymptomatic

Petechiae

Purpura

Mucosal Bleeding

Fatigue

How will labs appear for ITP

CBC = PTL < 100k

Smear = Normal

Coag = Normal

HIV = Neg

Hep C = Neg

How is ITP dx?

If other cells are effected (RBC / WBC), it is not ITP

Must exclude other medications and secondary

What is the goal of ITP tx

Safe PTL count

At what level can we montior an ITP patient without tx

30k

What are the first line treatment options for ITP

Steroids (PO / IV)

IVIG

What steroid is used for ITP

Dexamethasone PO

ITP being treated by steroids should see improvement by what time?

2 weeks

IV Immune Golbin (IVIG)

An agent that can rapidly increase PTL count

What are the indications for each first line treatment of ITP

Steroids = No active bleed

IVIG = Active bleed OR invasive surgery

What are the second line treatment options for ITP

Splenectomy

Rituximab

When do we use Rituximab for ITP

Poor Surgical Candidates

Refuses splenectomy

Poor Response to other tx

Bridge into Splenectomy

When do we give PTL transfusion for ITP

Life-threat bleeding

Thrombopoiesis Stimulating agents

Medications that increase PTL production in the body

Romiplostim

Thrombopoiesis Stimulating agent

Eltrombopag

Thrombopoiesis Stimulating agent

What is the risk of using Thrombopoiesis Stimulating agent

VTE

Microangiopathic Hemolytic Anemia (MAHA)

A type of anemia where small endothelium damage leads to PTL aggregation, intravascular hemolysis, and schistocytes

Schistocutes

Fragmented RBCs

What are macrovascular causes of schistocytes

Calcified Aortic Valve

Mechanical Cardiac Valve

What conditions present with MAHA

Hemolytic-Uremic Syndrome (HUS)

Thrombotic Thrombocytopenic Purpura (TTP)

Disseminated Intravascular Coagulation (DIC)

HELLP Syndrome

HELLP Syndrome

HTN in pregnancy complication

• Hemolysis

• Elevated Liver Enzymes

• Low PTL

How will labs appear for MAHAs

Hgb = Low

PTL = Low

Reticulocyte = High

Bili = High

Haptoglobin = Low / Absent

Bili Urine = Present

Smear = Schistocytes

LDH = High

Direct Coombs = Negative

Hemolytic Uremic Syndrome (HUS)

A condition in which microvascular clots cause:

• MAHA

• Thrombotic Microangiopathy (TMA)

• A decrease in renal function (Uremia)

Who mainly gets HUS

children < 5 years old

What is the leading cause of renal failure

HUS

What are the types of HUS

•Typical / Diarrhea-Positive HUS

•Atypical / Diarrhea-Negative HUS

What causes typical HUS

Shiga toxin-producing E. coli (STEC) O157:H7

Where is E. coli O157:H7 found

Contaminated milk and beef

What does STEC do in the body"?

•Toxin will get absorbed into blood and carried to the glomeruli

•Once there, it enters glomerulus endothelium and induce apoptosis

•Apoptosis will then trigger primary hemostasis

What are atypical causes of HUS

• Bacterial

  • S. pneumo

  • Salmonella

  • Campylobacter

  • Legionella

  • Mycoplasma

• Viral

  • HIV

  • Coxsackie

  • Influenza

  • EBV

  • HSV

• Medications

  • Quinine

  • Antiplatelets

  • OCPs

  • Chemo

• Autoimmunity

• Genetics

How does HUS present itself

Prodromal Gastroenteritis (Bloody Diarrhea + Abd Pain + Vomiting)

Acute Renal Failure / Anuria (2-3 days later)

Pallor

Jaundice

Petechiae

HTN

How do labs appear for HUS

Hgb = Low

PTL = Low

Reticulo = High

Bili = High

Bili Urine = Present

Haptoglobin = Low / Absent

Smear = Schistocytes

LDH = High

Direct Coombs = Negative

BUN / Creatinine = High

PT/INR = Normal

apTT = Normal

Stool Cx = E.coli O157:H7

Stool PCR = Shiga

Fibrionogen = Normal

D-Dimer = Normal

ADAMTS-13 = Normal

Urinalysis = Proteinuria + RBC / RBC casts

Urine Cx = STEC

How can HUS be prevented

Avoid antimotility agents for diarrheal illness

Avoid Abx to treat diarrheal illness

What is general treatment for HUS

Fluid Management

Transfusions

When do we give RBCs for HUS

Hgb < 6

When do we give PTLs to HUS

Significant symptoms

What do we do with AKI secondary to HUS

•Discontinue any nephrotoxic drugs

•Dialysis may be needed

What are the common electrolyte imbalances for HUS

Hyperkalemia, hyperphosphatemia, and metabolic acidosis

What tx is given for HUS that affects the CNS

C5 Complement Inhibtor

Plasma Exchange

Eculizumab

A C5 complement inhibtor

What vaccines should given prior to starting Eculizumab

Men A/B

H. flu

S. pneumo

When do we do plasma exchange for HUS

CNS Involvement + Complement Mediated

Thrombotic Thrombocytopenic Purpura (TTP)

A rare emergency that causes MAHA and TMA due to an ADAMSTS13 deficiency causing PTL microthrombi

What can cause TTP

Idiopathic acquired autoimmunity (#1)

Quinine

STEC

Congenital (RARE)

What is the presentation for TTP

• (Classic Pentad)

  • Thrombocytopenia

  • Renal Function Abnormality

  • MAHA

  • Neurologic

  • Fever

• Other S/S

  • Pallor

  • Jaundice

  • Petechiae

  • AMS

  • TIAs

  • Focal Neuor Defects

  • Uncommon Organomegaly

How will labs appear for TTP

Hgb = Low (<10)

PTL = Low (< 30k)

Reticulo = High

Bili = high

Haptoglobin = Low

Bili Urine = Present

Smear = Schistocytes

LDH = High

Direct Coombs = Negative

BUN / Creatinine = Normal to High

aPTT = Normal

PT / INR = Normal

Stool Cx = +/- E. coli O157:H7

Stool PCR = +/- Shiga

Fibrinogen = Normal

D-Dimer = Normal

Antithrombin = Normal

ADAMSTS-13 = Low (< 10 %) (Takes 7 days_

Urinalysis = Proteinuria + RBC / RBC Casts

Urine Cx = +/- STEC

What is 1st line tx for TTP

Plasma Exchange

Plasma Exchange

A combination treatment of plasmapheresis and plasma transfusion

How long should a TTP patient plasma exchange?

PTL count is fixed

AltDX

What are some adjunct tx for TTP high risk patients

Steroids

Rituximab

Caplacizumab (Cablivi)

Caplacizumab (Cablivi)

Monoclonal antibodies for vWF that blocks binding with GPIb

What is the indication for giving Caplacizumab (Cablivi) for TTP

Neuro Involvement

What is the second line therapy for TTP

Plasma Infusion using FFP

Why do we avoid PTL transfusion in TTP patients

CVA and MI risk

Disseminated Intravascular Coagulation (DIC)

•A systemic process causing both microvascular thrombosis and hemorrhage

What is the patho of DIC

Blood is exposed to procoagulants (Mainly TF)

Cascade activated forming thrombi from fibrin and PTL

Excessive thrombi production leads to depletion of factors, PTL, and anticoagulants (ATIII, Protein C, Protein S)

Fibrinolysis activates and generates FDPs

FDPs interfere with fibrin clot formation and platelet aggregation at GPIIb/IIIa

Tissue damage results from reduced perfusion or bleed

What causes DIC

Sepsis (#1)

Malignancy

Trauma

HELLP Syndrome

Eclampsia

Septic Abortion

Extensive Surgery

How does acute DIC present

Hx of Trauma / Sepsis / Malignancy

Sudden Onset Bleeds from 3 unrelated sites

Petechaie

Ecchymosis

Oozing from Wound Site / IV Lines / Caths

Renal Dysfunction

Hepatic Dysfunction (Jaundice_

Respiratory Dysfunction (Hemoptysis)

Neurolgoic Dysfunction (Coma / Delirium / Focal Neuro)

Shock

How do labs appear in DIC

Hgb = Low

PTL = Low

Reticulo = High

Bili = High

Haptoglobin = Low

Bili Urine = Present

Smear = Schistocytes

LDH = High

Coombs = Negative

ADMATS13 = Normal

aPTT = Prlonged

PT / INR = Prolonged

TT = Prolonged

D-Dimer = High

FDP = High

Fibrinogen = Low

VII = Low

X = Low

Prothrombin = Low

Antithrombin = Low

Protein C / S = Low

How is DIC tx

Treat Underlying

Hemodynamic Support

When do give PRBC for DIC

Hgb < 7

When do give PTLs for DIC

PTL < 10k w/o bleed

PTL < 50k w/ bleed

What should given to a DIC patient who is bleeding and has prolonged coag

FFP or Cyroprecipitate

If a clot is identified in DIC, what is given>

Heparin

Heparin Induced Thrombocytopenia

•complication resulting from heparin exposure

What are the types of HIT

HIT-I

HIT-II or HITT

HIT-I

A direct effect of hparin on PTL activitation

How does HIT-I affect kabs

Slight fall in PTL (nadir 100k)

How is HIT-I tx

Nothing

HITT

an immune mediated condition where HIT Ab are made against heparin-platelet factor 4 complex

What are the risk factor for HITT

Surgery

Unfractionated Heparin > LMWH

Female

Older Age

How does HITT present

PTL decreased within 4-10 days of heparin

PTL < 150k

VTE is common

Arterial Thrombi possible (CVA / MI)

Lesion at injection site

Uncommon bleed

4TS Score

An assessment tool for HITT

How is 4TS Score taken

Thrombocytopenia

>50% fall or PTL lowest > 20x10^9 = 2

30-50% fall or nadir 10-19x10^9 = 1

<30 % or nadir < 10x10^9 = 0

Timing of PTL decrease

Day 5-10 or < 1day with recent heparin in last 30 days = 2

> Day 10 or < 1 day with heparin within 30-100 days = 1

< Day 4 = 0

Thrombosis or Sequelae

Thrombosis / Skin Necrosis / Systemic Reaction after Heparin = 2

Silent Thrombosis / Erythamatous Skin Lesions = 1

None = 0

Other Causes

None = 2

Possible = 1

Definite = 0’

Result

0-3 = Low risk

4-5 = Intermediate risk

6-8 = High risk

What is most commonly used test for HITT dx

Heparin-PF4 Ab ELISA

•Heparin-PF4 Ab ELISA

A test that detect Ab for Heparin-PF4

Test for HITT

Why is •Heparin-PF4 Ab ELISA not test of choice for HITT

False positive

What is gold standard test for HITT

Serotonin Release Assay

Serotonin Release Assay

A test where serum is incubated with donor PTL, heparin, and radiolabeled serotonin to see if PTLs are getting activated by Ab in the patient serum

Heparin Induced Platelet Aggregation (HIPA) Assay

Serum is added to donor plasma with varied concentrations of heparin

•+ = Minimal agglutination in presence of low / Significant agglutination in presence of high

Tests for HITT

What is the tx for HITT

Stop heparin

Start non-heparin anticoagulant

Parenteral Diect Thrombin Inhibitors

Argatroban (Acova)

Parenteral Direct Thrombin Inhibitor

Bivalirudin (Angiomax)

Parenteral Direct Thrombin Inhibitor

How do we montior direct thrombin inhibtors

aPTT