HEMATOLOGY/

IMMUNOLOGY REVIEW

 Anemia

 Coagulopathies

 ITP, DIC, HIT

 Immune deficiencies

 Leukopenia

 Thrombocytopenia

Disseminated Intravascular Coagulation (DIC)

 Hypercoagulation secondary to widespread

endothelial damage

 Use up all the clotting factors, then you bleed!

 Microvascular thrombus formation

 Trauma

 Sepsis/Infection

 Obstetric Complications

 Release if procoagulants  activate the clotting

cascade

 Intravascular fibrin formation

Clinical Presentation

 Similar to ARDS

 Bleeding from multiple

sites in the body

 Ecchymosis &

symmetrical necrosis of

limbs

 Purpura Fulminans

 Gums / mucous

membranes

Diagnosis:

 Predisposing condition

 Lab values indicate widespread

coagulation deficits

 ↓ Platelets < 50,000

 ↑ D-dimer 1 – 5, adv. > 5

 ↓ Fibrinogen < 100

 ↓ Prothrombin Index

40 – 70, < 40

 ↑ PTT/PT

“Consumptive Coagulopathy”

 Advanced DIC has a

mortality up to 80%

 Treatment: **treat the

cause

 Treat bleeding:

 Platelet transfusion

 Cryoprecipitate

 Heparin – ineffective;

abandoned

> 5 – Consistent with DIC

Heparin Induced Thrombocytopenia (HIT)

 Platelet count ↓ by ≥

50% within 5 – 10 days

of exposure to Heparin

 May develop more

quickly if previous

exposure to Heparin

 Erythematous lesions

around SQ injection sites

 25% develop systemic

reaction

 Fever

 Chills

 Tachypnea

 Tachycardia

Thrombosis

 **Major Complication**

 75% of cases develop

systemic Thrombosis

 50% DVT of lower

extremity

 10% DVT of upper

extremity

 25% Pulmonary embolus

 Arterial Thrombosis

 AMI & Stroke

 Risk is greater with

unfractionated Heparin

(UFH)

 Orthopedic surgery 3 – 5%

 Cardiac Surgery 1 – 3%

 Medical Patients 1%

 LMWH ~ 1% Risk of

developing HIT

 Even low doses & heparin

flushes!!!

 Don’t forget: Heparin

coated catheters!!!

Diagnosis of HIT

 Clinical exposure to Heparin

 Thrombocytopenia

 Symptomatic Thrombosis

 IGG Antibodies to Heparin

 Platelet Factor 4 complex

 Antibody Assay

 Clinical picture + Assay for

Diagnosis

Treatment HIT

 Discontinue all forms of

Heparin!!!

 Anticoagulation Direct Thrombin

Inhibitors

 Lepirudin

 Cleared by kidneys

 0.4 mg/kg IV, then 0.15

mg/kg/hr (Max 110 kg weight)

 PTT 1.5 – 3x control

 Argatroban

 Cleared by Liver

 2 mcg/kg/min – Max 10

mcg/kg/min

 PTT 1.5 – 3x control

 Long term anticoagulation

with Coumadin

 HOWEVER, do not use

during the active phase of

HIT

 Increased risk of limb

gangrene

 Heparin antibodies last >

100 days after exposure

 Do not reintroduce

Heparin as long as

antibodies persist!

Platelet Disorders

Either:

 Not enough platelets

 Impaired function

 Life span of a platelet is

10 days

 Any endothelial damage

causes platelets to adhere

to collagen

 Release of calcium 

 Activation of Glycoprotein

IIb/IIIa receptors on the

surface of platelets 

 GP IIb/IIIa receptors bind

to fibrinogen to form

bridges to other platelets to

form clots 

 Calcium activates the

coagulation cascade

 End result  thrombus

Thrombocytopenia

 Platelets < 150,000

uL

 The body can form

platelet plugs until <

100,000 uL

 Without a structural

lesion, we can tolerate

platelet count ~ 5,000

uL without major

bleeding

 In ICUs, the incidence is

up to 35%

 Sepsis

 Phagocytosis of

platelets by

macrophages

 DIC

Many medications cause impaired platelet function

 ASA

 Clopidogrel

 Prasugrel

 Pradaxa

 Glycoprotein inhibitors

 Ticlidopine

 PCN

 Cephalosporin

 Alteplase

 Heparin

 Diphenhydramine

 Calcium Channel

Blockers

 Nitroglycerin

 Nitroprusside

 Dextran

 Haloperidol

 Ketorolac

 Warfarin (Coumadin)

 Acts on extrinsic & common

coagulation pathways

 Monitor PT/INR

 Goal INR 2 – 3

 DVT Prophylaxis

 PE Prophylaxis/treatment

 Atrial fibrillation

 Goal INR 2.5 – 3.5

 Mechanical prosthetic

valves

 Reversal: Vitamin K

 Heparin (unfractionated)

 Acts on intrinsic & common

coagulation pathways

 Monitor aPTT

 Normal 25 – 38 seconds

 For sheath removal, can also

monitor ACT

 Therapeutic ACT 300 – 350

seconds

 Discontinue sheath when ACT

< 150 seconds

 Reversal: Protamine

Low Molecular Weight Heparin vs.

Unfractionated

LMWH:

 Less incidence of HIT

 No need to monitor aPTT

 No monitoring

 Longer half-life

 4 – 6 hours vs. 1 – 2 hours

 More predictable d/t bioavailability

 90% bioavailable vs. 30%

Platelet Transfusions

 Pooled

1. RBCs separated by

centrifuge

2. Platelet rich plasma

centrifuged at high speed

3. Platelets are separated

with leukocytes

 Increased incidence of

fever with platelet

transfusion

 Store up to 7 days

 Viability decreases after 3

days

 4 pack platelets

 20,000/uL rise

 6 pack platelets

 30,000/uL rise

 1 hour after transfusion,

lasts 8 days

Platelet Transfusion con’t

If not seeing an increase in the platelet count with a

transfusion:

 Leukocyte reduced

 ABO compatibility

Anemia: Who’s at Risk?

 Anyone in the ICU > 7

days

 2 biggest reasons for

anemia:

 Frequent phlebotomy

 Systemic inflammation

 RBC production is

regulated by

erythropoietin

 Transfusion threshold….

It depends!!!

 Generally Hgb < 7

g/dL

 CAD, AMI

 Debate to use Oxygen

extraction as a

transfusion trigger

 > 50% O2 extraction

 O2 sat – venous O2 sat

Blood Products

 PRBCs

 Stored at 4°C – 21 day shelf life

 CPD preservative

 Citrate

 Binds to calcium – anticoagulant

 Monitor Calcium levels!

 Patient will need 500 – 1 Gram of

Ca for every 3 – 4 units of PRBCs

 Phosphate

 Slows breakdown of 2,3-DPG

 Banked blood low in 2,3-DPG

 2,3 DPG encourages unloading

between O2 & hemoglobin

 Dextrose

 Fuel source for electrolytes

 Whole blood is rarely

used

Spun down to:

 Erythrocytes

 PRBCs

 200 mls of cells

 50 – 100 mls of CPD &

plasma

 Plasma

Blood Products con’t

 Leukocyte - reduced

 Hx: febrile hemolytic

transfusion reactions

 30% of leukocytes still

remain

 Washed RBCs

 Reduce leukocytes &

plasma

 Reduces reactions from

plasma proteins

 Universal Donor

 O Negative

 Universal Recipient

 AB

 Only use normal

saline…why not Lactated

Ringers?

 LR contains Calcium that

can promote clotting!!!

Hemolytic Reactions

 Usually human error

 ABO compatibility

 5 mls to see a reaction

 Signs:

 Fever

 Tachycardia or

bradycardia

 Dyspnea

 Chest pain

 Low back pain

 Hypotension

 Blood in urine

Treatment:

 Stop the transfusion

immediately!!!

 Morbidity/Mortality r/t

the amount of blood

received

 Monitor VS/BP

 Infuse fluids – Support BP

 Send unit to the BB

 Coomb’s Test – Positive

reaction

In general…

 Anemia is tolerated as long as intravascular volume

is adequate!!!

 Hemoglobin & Hematocrit tell you very little about

oxygen utilization!

Novel Oral Anticoagulation (NOACs)

 Pradaxa (dabigatran)

 Non-Valvular atrial fib, VTE Prophylaxis

 Half-life 12 – 14 hours

 Xarelto (rivaroxaban) – Direct Factor Xa Inhibitor

 Non-Valvular afib, VTE prevention

 Savaysa, Lixiana (edoxaban) – Direct Factor Xa Inhibitor

 VTE Prophylaxis after ortho surgery, stroke prevention

 Eliquis (apixiban) – Direct Factor Xa Inhibitor

 Venous thromboembolic events

 Currently, no reversal or antidote

 If ingested in < 2 hours, activated charcoal

 Otherwise, control bleeding