Download Hematologic Disorders in the ICU

Hematologic Disorders
in the ICU
Bradley J. Phillips, M.D.
Burn-Trauma-ICU
Adults & Pediatrics
CASE # 1
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78 yom with rest pain R foot, ABI’s L 0.6, R 0.25
PMH - PVD, COPD, HTN, ? Cirrhosis (EtOH)
PSH - R CEA ‘97, R 1st Toe Amp ‘98
Meds - Trental, Spirolactone, Inhalers
SH - EtOH quit ‘90, Smoker 50 pk yrs. quit ‘95
PE - ruddy complexion, L CEA scar, distant BS,
mildly distended abd, R foot cool
Pulses 1+ R fem, doppler only R Pop/DT/PT
CASE # 1
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Angiogram - severe plaque R ext iliac, occluded
SFA, patent AK popliteal artery with marginal
runoff via posterior tibia artery
Labs - Plts 100K, Hct 30, INR 1.4, PTT 40, Tbil 2.1
OR - exploration of R iliac with endarterectomy,
femoral to AK popliteal bypass with reversed vein
Blood Loss (intraop) 3 liters, given 6 units PRBC
Postop - transferred to ICU, pulmonary toilet,
heparin qtt for graft patency
CASE # 1
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Uneventful recovery until day 5, plt count dropped to
60 K, then 30 K the next day
Developed protracted bleeding from venopuncture
sites and mild hematuria
HO transfused 6 units plts, but bleeding continued
? Cause of hemorrhage ?
? Evaluation (ie. exam, labs) ?
? Plan of treatment ?
CASE # 1
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Plan
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Coagulation studies
• R/O DIC
• Exclude excessive anticoagulation with heparin
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LFT’s - R/O worsening liver dysfunction
R/O Sepsis
• Blood cultures
• ? Broad-spectrum antibiotics
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R/O drug reaction
? Dilutional or consumptional thrombocytopenia
? Bone marrow aspiration
Case # 1 - Workup
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Blood smear - thrombocytopenia, no
fragmentation RBC
Coags - PTT 13 s, PTT 50 s, FDP < 4 mg/l
LFT’s - no significant changes from pre-op
Blood cultures draw - initial read negative
DX : HIT confirmed by heparin antibody
Hemostasis
Liver Disease
Nature of Abnormalities
Decreased and abnormal
proteinsIntravascular consumption of
factors Delayed clearance of activated
products
Underlying liver disease
Severity of disease
Speed of onset of impairment
Liver
Minimal generation of
thrombin and plasmin
Endothelium
Bone Marrow
Thrombocytopenia (ICU)
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Causes (Common)
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Lab error - clumping
secondary to EDTA in
test tube, need smear to
exam
Sepsis
Peripherial consumption
Dilutional
Disseminated
intravascular coagulation
(DIC)
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Causes (Uncommon)
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Liver Disease
Hypersplenism
Bone marrow failure
Drugs ( ie heparin,
immunosuppressives,
antibiotics)
Viruses
Rare diseases in surgical
patients (TTP, ITP)
DIC
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Intravascular thrombin generated leads to
consumption of both coagulation factors
and platelets with secondary fibrinolysis
releasing fibrin degradation products
 Severe thrombocytopenia, coagulopathy
DIC - Etiology
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Increased Tissue Factor
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Injured tissue
• trauma
• tissue necrosis
• burns
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Stimulated monocytes or
endothelial cells
• endotoxin
• cell wall polysaccharides
• immune complexes
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Endothelial sloughing from
acidosis ( pH < 7.2 , fully
heparinized blood clots)
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Thrombogenic
Phospholipids
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Obstetric disorders
• abruptio placentae
• eclampsia
• amniotic fluid embolism
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Intravascular hemolysis
• transfusion reactions
• infections
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Ascitic fluid
• Leveen or Denver shunts
Clinical Presentation
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Bleeding
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More pronounced in liver
disease
Wound bleeding
Waterhouse-Friderichsen
Syndrome
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Thrombosis
(microvascular)
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Organs at risk
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Lungs (ARDS)
Kidneys (ARF)
Liver
Cardiac (MI)
Brain (stroke)
Purpura fulminans
• gangrene of digits or
skin necrosis
DIC – Lab Findings
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Lab findings
 Procoagulant and fibrinolytic activation
 Reduced protein C and S activity
 Fibrin degradation products (FDP)
 Biochemical evidence of end organ dysfunction
 Low-grade DIC - near normal labs
 Trousseau’s syndrome
 Subacute bleeding (qualitative platelet defect from
FDP)
DIC
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Laboratory findings
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Fribinolysis
• FDP - measures fibrinogen and fibrin ( 85-100%)
• D-dimer - measures plasmin degradation of crosslinked fibrin only ( 90%)
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PT (unreliable) - prolonged in 50 - 75%
PTT (unreliable) - prolonged in 50%
Platelets usually low
Blood smear (schistocytes)
DIC
 Management
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Identify and treat underlying condition
Supportive care
If condition rapidly reversible, watch and wait, use
FFP and platelets as needed
Stop microvascular thrombosis
• consider heparin, tPA, or urokinase
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surgical intact vascular system
actual or potentially serious bleeding or clotting
Not rapidly reversible
Control bleeding, use FFP and platelets as needed
Heparin Induced Thrombocytopenia
(HIT)
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Heparin-dependent IgG antibodies which bind
platelet-bound heparin through specific antigen
binding
Antibody Fc region then either binds complement
or receptor on platelet membrance causing
platelet activation and in vivo aggregation, in
some causing thrombus formation
Thrombocytopenia >> thrombosis
Thrombosis = higher mortality
Incidence 0.5 to 5.0 %
HIT - Diagnosis
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Seen 5-12 days or more after treatment
 Not dose-dependent, increased risk with length of
treatment
 Platelet count < 100 K
 Diagnosis
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follow platelet count daily 3-5 days
in vitro platelet aggregation studies (heparin antibody)
HIT - Treatment
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Treatment
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Stop heparin
Danaparoid - immediate anticoagulant
• cross reacts with plt factor 4 in 10% of cases
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Ancrod - snake venom enzyme
• no cross-reactivity, take 12 hours to onset
• contraindicated in sepsis and DIC
CASE # 2
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46 yom motorcyle vs car, + EtOH
 Hypotension in the field BP 90/P
 Arrival to trauma bay
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Airway patent, Breath sounds ok (RR 22)
BP 90/P, HR 110
Alert and oriented
Given 2L of saline, BP 95/P
Complaining of L sided abdominal pain
FAST - positive fluid LUQ
OR - exploratory lap, 1.5 L of blood, shattered spleen,
omental bleeding, liver laceration L lat lobe
CASE # 2
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Perform splenectomy, controlled bleeding, repair
liver lac, place JP under L liver lobe, EBL 4 L
Given intraop - 10 u PRBC, 3 FFP
Transferred to SICU, Hgb 10, P 76, BP 120/75
Blood stain fluid from liver bed JP drain, next 3 hrs
400 cc
Pulse gradually increased to 110, BP 100/60 despite
2 u PRBC
Labs
 Hgb 8.0, PT 32 sec, PTT 65 sec, Platelets 70K
? Plan ?
CASE # 2
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Blood products given
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Two hours
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10 U FFP
2 U PRBC
450 ml of blood-stained fluid from abdominal
drain
? Etiology of Bleeding ?
 ? Plan ?
CASE # 2
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Further coagulation test ordered
 Patient reexamined
 Labs
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Hgb 8.0, PT 17, PTT 42, FDP 4, Plt 84K
Cr 1.7, BUN 32
? PLAN ?
CASE # 2
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Given
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10 U FFP
6 U Cryoprecipitate
6 U Platelets
2 u PRBC
Continued bleeding from abdominal drain
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Evaluation and Management
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First step
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Resuscitation and establish cause of bleeding
Blood volume should be increased to
maintain tissue perfusion, rather than a
normal hemoglobin concentration
 Hgb useful as an index of hemorrhage as
some blood loss may be concealed
Etiology
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Surgical Cause (missed injury, local hemostatic failure)
Acquired disorder of hemostasis
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Drugs ( ie. ASA, heparin flushes)
Uremia
Dilutional effect ( massive blood loss or transfusion)
Consumption (sepsis or poor tissue perfusion)
Anemia
DIC
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Liver disease
 Pre-existing herditary hemorrhagic disorder
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Mild hemophilia (Christmas factor)
von Willebrand;s disease
variety of platelet defects
CASE # 2
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Bleeding is prolonged by anemia
 progressive anemia may contribute to the bleeding
tendency
 ? Related to platelet-endothelial interaction at high
shear rates with less interaction at low hematocrits
No clinical evidence of pre-existing coagulapathy
No drugs given to impair hemostasis
Protracted bleeding from isolated site - no bleeding at
venipuncture sites, ET tube, abdominal wound
Mild coagulopathy documented with prolongation of PT
and PTT but corrected with FFP
DX: Surgical bleeding, re-exploration revealed 2 L of
blood, bleeding short gastric artery
CASE # 3
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53 yof with a three -year h/o menorrhagia
admitted for elected TAH
On admission her Hgb was 9.0 with MCV 75
She was taken FeSO4 200 mg/d but no other
medications
No significant PMH
Three healthy children
In view of her anemia, her OB/GYN postponed her
surgery and transfused her 3 u PRBC
Case # 3
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On the day of surgery, she was found to be unwell,
T 39.0 , pulse 105 and BP 105/60.
On PE no apparent vaginal blood loss or
hemorrhage elsewhere
IVF were started and patient transferred to SICU
where she was noted to have macroscopic
hematuria
CASE # 3
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Given 1.5 L of saline, HR 90, BP 115/60
LAB’s
 Hgb 6.2, normal PT and PTT
 Creatinine 1.2
Urology was consulted for cystoscopy
4 U of PRBC were cross-matched for
transfusion, but two where found incompatible
and the cystoscopy was cancelled
? DX ?
? Incidence ?
CASE # 3
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DX - delayed hemolytic transfusion reaction
with intravascular hemolysis causing
hemoglobinuria
 Blood sample should be taken
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direct coomb’s
determination of specificity of the antibody for
incompatibility
serum bilirubin
Moderate hypochromic anemia on admission
likely result of iron deficiency
Indications for Transfusions
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Hemoglobin concentration is a determinant of
arterial oxygen concentration
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RBC infusion used to improve oxygen delivery
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CaO2 = HGB x O2 sat x 1.34 + PaO2 x 0.0031
DO2 = CI x CaO2 x 10
Animal experiments show that tissue oxygen
extraction is maintained with an 80% reduction in
red cell mass, so long as blood volume and blood
flow are maintained
Indications for Transfusions
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In critical ill patients impaired tissue oxygen
extraction may occur and red cell transfusion
may not result in any improvement in tissue
oxygen metabolism
 Traditionally, patient for elective surgery
transfused for Hgb< 10, Now data shows no
difference in mortality if Hgb > 7 if euvolemic
Risks of Transfusion of RBC
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 Infectious
Hepatitis A
Rare
Hepatitis B
1/100,000
Hepatitis C
1/120,000
HIV
1/1,000,000
Creutzfeld-Jacob none
CMV
1/4,000,000
Bacterial
1/1,000,000
Syhillis
Rare
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Non-infectious
Fever
1-2%
 Urticaria
1%
 Hemolytic
1/6000
 Fatal hemolytic 1/100,000
Hemolytic Transfusion Reaction
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Signs and symptoms
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Laboratory results
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fever, chills, headache, chest pain, anxiety, respiratory
distress
free Hgb in plasma
Hemoglobinuria
Decreased haptoglobin
Increased creatinine and ARF ( lysis of RBC membranes
in golmerulus)
Fatal transfusion reactions are usually secondary to
clerical error that results in giving the wrong blood
to a particular patient
Questions…?