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Anemia and The Bleeding
Patient
November 1, 2005
Eli Denney D.O.
Definition of Anemia
 Anemia – a reduced concentration of red
blood cells. Measured by Hct, Hgb and RBC
count.
 Anything that reduces production or
increases destruction will result in anemia if
the processes are not corrected.
Anemia - Causes
 Most common causes in U.S.
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Iron deficiency
Thalassemia
Anemia of Chronic Disease
Physiologic Reactions to Blood Loss
 Acute – Peripheral vasoconstriction and
central vasodilatation
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If blood loss continues – small vessel
dilatation with compensatory decreased PVR,
resulting in increased CO.
 Chronic - Increased plasma volume keeps
intravascular volume normal
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Erythropoietin released by kidneys –
reticulocytes in 3-7 days.
Signs and Symptoms
 Depend upon
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Rate of blood loss
Amount of blood lost
Age
Overall Health
Comorbid disease states
Signs and Symptoms
 Weakness
 Palpitations
 Fatigue
 Orthostatic
 Dyspnea
symptoms
 Lethargy
Physical Exam Findings
 + Orthostatic BP’s
 Widened pulse
 Tachycardia
pressure
 GI bleeding/Uterine
bleeding
 Altered Mental Status
 Pallor
 Systolic ejc. murmur
Diagnosis
 Confirmed by lab values – RBC count, Hgb
and Hct.
 CBC may not determine specific cause –
need to obtain other labs to begin appropriate
workup
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CBC-provides RBC indices (MCV)
Reticulocyte count
Peripheral smear
Iron studies
Folate, B12 levels
Treatment
 In ED, anemia from hemorrhage is the most
common need for treatment
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Symptomatic
Hemodynamically unstable
Asymptomatic - can do outpatient work up depends upon clinical situation.
 Based on clinical situation, patients should be
typed and cross-matched for transfusion
 Admit Patients with ongoing blood loss for
definitive care
Increased Likelihood of Bleeding
Disorder
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Spontaneous bleeding-multiple sites
Bleeding from untraumatized sites
Bleeding several hours after trauma
Bleeding into deep tissues or joints
Family history of bleeding disorder
Excessive bleeding after dental extractions or
surgical procedures
 Liver disease
Increased Likelihood of Bleeding
Disorder
 Drugs –
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Ethanol
Coumadin
ASA
NSAIDS
Antibiotics
Plavix
Bleeding Site May Indicate Specific
Abnormalities Indicative of Platelet
Disorder
 Mucocutaneous Bleeding
 Petechiae
 Ecchymosis
 Epistaxis
 GI/GU bleeding
 Heavy menstrual bleeding
 Purpura are associated with
thrombocytopenia and commonly indicates a
systemic disease
Coagulation Factor Deficiencies
 Bleeding into joints, potential spaces,
retroperitoneum and delayed bleeding
 Mucocutaneous bleeding and bleeding into
deep spaces may be signs of DIC – both
pathways of homeostasis are involved.
Normal Coagulation
 Platelet Plug (Primary Homeostasis)
 Cross-linked Fibrin (Secondary Homeostasis)
 Fibrinolytic system – counter regulatory
system that prevents excessive clot
formation.
Primary Homeostasis
 Depends upon platelet interaction with
endothelium
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Requires normal vascular endothelium,
functional platelets, von Willebrand factor, and
normal fibrinogen
von Willebrand factor connects platelets to the
endothelium by glycoprotein Ia
Fibrinogen connects platelets by glycoproteins
IIB-IIIA.
Secondary Homeostasis
 See Fig 218-3 - Coagulation Cascade
Fibrinolytic System
 Purpose is to limit the size of fibrin clots
 Endothelial cells release tPA which converts
plasminogen to plasmin which is already a
part of the fibrin clot
 Plasmin degrades fibrinogen and fibrin
monomer into fibrin degredation products and
cross linked fibrin into D-Dimers
Other Inhibitory Proteins
 Antithrombin III – inhibits clotting cascade.
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Inhibits function of XIIa, XIa, IXa and
Thrombin.
Heparin potentiates this interaction.
Proteins C and S
 Activated Protein C – binds with cell surface
bound Protein S – the bound proteins inhibit
factors Va and VIIa.
Inhibitory Proteins
 Deficiencies or dysfunction of proteins C,S or
antithrombin III can cause a hypercoagulable
state.
Initial Testing for Bleeding Disorders
 CBC
 PT/INR
 PTT
 Further testing as indicated (Table 218-4)
Acquired Bleeding Disorders
Acquired Platelet Defects
 Quantitative Defects
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Decreased production
Increased destruction
Splenic sequestration
 Platelet levels less than 10-20,000 / microL
increases the likelihood of spontaneous
bleeding – especially intracranial
 Levels less than 10,000 – transfusion of
platelets will be necessary
Decreased Production
 Bone marrow infiltration
 Aplastic anemia
 Viral infections – CMV, Rubella
 Drugs (Thiazides, Ethanol, Chemo-agents)
 Vitamin B12, Folate deficiency
 Radiation
Increased Destruction
 ITP
 Viral infections –
 TTP
HIV, Varicella, EBV
 Drugs –
Heparin/Protamine
 HUS
 DIC
Idiopathic Thrombocytopenic Purpura
 Autoimmune disease involving
thrombocytopenia, purpura or petechiae,
normal bone marrow function and no other
known cause for decreased platelets.
 Autoantibodies attach to circulating platelets
and are destroyed by the reticulendothelial
system.
 Platelets function normally despite low
numbers and bound with antibodies
ITP – Acute and Chronic Course
 Acute – typically occurs in children, males =
females, duration 1-2 months.
 Chronic – typically occurs in adults, lasts
greater than 3 months, female > male,
resolution unlikely even with treatment.
 Patients with chronic ITP more commonly
have another disease or autoimmune
disorder.
ITP – PE and Lab
 Commonly PE will show petechiae, epistaxis,
gingival bleeding, bruising, and possible
menorrhagia. Remaining PE may be normal.
 Lab – CBC - low platelets, otherwise normal.
Peripheral smear-normal platelets, few in
number
 If history, PE, and above lab support the
diagnosis of ITP, no further ED testing is
necessary.
Treatment - ITP
 Minimize bleeding risks – Meds, falls,
comorbid disease states and procedures.
 Asymptomatic and healthy, with platelet
counts > 50,000 – no treatment is needed
 < 50,000 and symptoms require treatment
 <20,000-30,000 require treatment
Treatment - ITP
 Prednisone 60-100 mg/d – tapered after platelet
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count returns to normal ranges.
If steroid therapy fails – splenectomy – produces
remission in 65 percent of patients.
If bleeding is life threatening – local hemorrhage
control should instituted and high dose
methylprednisolone 1-2 g/d for 2-3 days used.
Intravenous immunoglobulin as needed.
Platelets transfused after steroids or immunoglobins.
Drug Induced Thrombocytopenia –
Table 219-2
 Common drugs
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Heparin
Sulfas
ASA
Ethanol
Thiazides
Indomethacin
Valproic Acid
Lasix
Platelet Sequestration
 Splenomegaly and thrombocytopenia without
significant bleeding is not uncommon.
Another bleeding disorder is usually involved
if significant hemorrhage is present.
 Splenectomy is the definitive therapy for
patients with low counts and evidence of
significant hemorrhage.
Qualitative Platelet Abnormalities
 Liver disease
 Myeloprolifertive
 Uremia
disorders
 Dysproteinemias
 Von Willebrands
disease
 Leukemias
 DIC
 SLE
 ITP
 Cardiopulmonary
Bypass
Drug Induced Platelet Dysfunction
 ASA
 NSAIDS
 Clopidogrel
 Ticlopidine
Liver Disease
 Any disease that affects the hepatocytes can
affect the production of the clotting factors
 Malabsorption of Vit. K by primary biliary
cirrhosis and intra and extrahepatic
cholestasis will affect factor II, VII, IV, and X
 In more severe liver disease, decreased
synthesis of a2 plasmin inhibitor will cause a
general state of fibrinolysis and increase DDimers and fibrin degradation products
Lab
 To evaluate coagulation in liver disease the
following labs will need to be ordered
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Hematocrit
PT
aPTT
Platelet count
FDP and D-Dimer
Treatment
 Lab abnormalities without bleeding – patients
can be observed
 Bleeding or invasive procedure needed –
treatment is necessary
 Vitamin K for liver disease
 FFP if prolongation of PT and aPTT
 Cryopercipatate if fibrinogen levels < 100
mg/dL
 Platelet transfusion if indicated - <10,000
Renal Disease
 Dialysis related thrombocytopenia
 Toxin inhibition of platelet aggregation –
uremic toxins.
 For life threatening bleeding, treatment is
usually dialysis and transfusion for anemia,
DDAVP and conjugated estrogens.
 Platelet transfusion and cryoprecipitate
transfusions as needed.
Disseminated Intravascular
Coagulation
 DIC – an acquired syndrome characterized
by activation of the coagulation system
resulting in fibrin formation. The fibrinolytic
system is also activated which breaks down
clots, uses all coagulation proteins and
results in bleeding - Tintinalli
 DIC is associated with many conditions –
Table 219-5
Pathophysiology
 Disease process begins by the activation of tissue
factor – extrinsic pathway.
 Thrombin converts fibrinogen to fibrin leading to
formation of small clots that are deposited in
capillaries causing tissue ischemia – organ
dysfunction.
 Excessive activation of the coagulation system leads
to depletion of coagulation proteins and platelets.
 tPA is activated indirectly by thrombin and fibrin and
the fibrinolytic system is activated – in DIC the
system works in excess and can result in
uncontrolled bleeding
DIC Manifestations
 Hemorrhage and thrombosis both take place,
one form usually is dominate.
 Hemorrhage – most dominate
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Petechiae
Ecchymoses
GI/GU bleeding
Wounds/IV sites
DIC Manifestation
 Thrombosis
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Purpura fulminans
Mental Status Changes
MOF
Oliguria
ARDS
Tissue necrosis
 In chronic DIC the liver produces enough
coagulation proteins to compensate
DIC - Lab
 Increased PT
 Thrombocytopenia – most common
 Low fibrinogen levels
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Fibrinogen levels less than 100 mg/dL, - more
likely to see bleeding complications
 D-Dimers are more specific than FDPs in
diagnosing DIC
 Increased LDH, decreased haptoglobin,
schistocytes on peripheral smear
DIC Treatment
 Treatment of underlying disease triggering DIC
 Hemodynamic support as needed –PRBCs, IVFs,
vasopressors as needed.
 Supplementation of coagulation proteins, platelets
and fibrinogen
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Cryoprecipitate in 10-unit doses to keep fibrinogen to
100-150 mg/dL
Platelet transfusion if < 20,000 or < 50,000 with
bleeding
FFP transfused at 10-15 mL/kg to replace clotting
proteins
Vitamin K, Folate
DIC Treatment
 Heparin for thrombotic dominant DIC or
chronic DIC and known clots –purpura
fulminans
 Antifibrinolytic agents are withheld for proven
hypofibrinogenemia and fibrinolysis. Heparin
should be infused before to decrease chance
of thrombosis
HIV Bleeding Disorders
 Thrombocytopenia is one of the earliest signs
of HIV infection
 Bleeding problems are uncommon, the most
common problems being bruising, mucosal
bleeding and petechiae
 Thrombocytopenia caused by
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Increased destruction – immune complex
related and HIV medications
Decreased synthesis – immune complex
related and HIV medications
HIV Bleeding Disorders
 HIV patients commonly have
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Lupus anticoagulant – increased aPTT, which
may appear and disappear with infection
Anticardiolipin antibody – rarely causes a
disorder in itself
Circulating Anticoagulants
 Antibodies that affect coagulation factors
 Known inhibitors for each coagulation protein
exist but the two most common are
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Factor VII inhibitors
Antiphospholipid antibodies – lupus
anticoagulant and anticardiolipin antibodies.
Factor VIII Inhibitors
 Can develop at any time but usually affect
patients with hemophilia A
 Patients at risk of developing factor VIII
inhibitors
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Elderly
Postpartum patients
Autoimmune disorders – SLE, RA, UC, Mult.
Myeloma
Have drug reactions – PCNs, Sulfas,
Phenytoin
Factor VIII Inhibitors
 Signs and Symptoms
 Large bruising without trauma
 Ecchymoses
 Hematomas
 Lab
 Normal PT
 Normal Thrombin clotting time
 Prolonged aPTT – does not correct after
mixing
 Factor VIII assay will be low
Factor VIII Inhibitors
 Treatment of Bleeding Episodes
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Pressure to bleeding site
Factor VIII concentrates
Factor IX complex concentrates
Prothrombin complex concentrates
Recombinant factor VIIIa concentrates
Plasmaphersis
Ultimately a hematologist should direct care
for life or limb threatening bleeding episodes
Antiphospholipid Antibody Syndrome
 Presence of lupus anticoagulant or
anticardiolipin antibodies, plus one or both of
the following: thrombosis and/or
complications with pregnancy (recurring fatal
loss <34 weeks)
Antiphospholipid Antibody Syndrome
 In reality SLE patients rarely have the
antibody (5-15 percent) in vivo patients
develop clots rather than bleed.
 Lupus anticoagulant more common in HIV
patients, cancer, drug reactions and other
autoimmune disorders
 Anticardiolipin antibodies commonly occur
with lupus anticoagulant but both can occur
separately
Antiphospholipid Antibody Syndrome
 Lupus anticoagulant lab abnormalities
 Normal or prolonged PT
 Prolonged aPTT – does not correct when mixed
 Normal Thrombin clotting time
 Patients may develop antibodies to prothrombin
causing a deficiency – suggested by markedly
prolonged PT
 Factor assays – all factors will be mildly low
 Russell viper venom time – detects presence of lupus
anticoagulant
 Anticardiolipin antibodies detected by ELISA assay
Antiphospholipid Antibody Syndrome
 Signs and Symptoms
 Thromboembolism – venous > arterial
 Pregnancy complications
 Thrombocytopenia
 Patients who develop thrombosis and remain
positive for lupus anticoagulant have a 50
percent chance of another clot forming within
2 years
 Recurrent fetal loss most likely due to
thrombosis of placental vessels
Antiphospholipid Antibody Syndrome
 Treatment
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Asymptomatic – observation, reduce risks for
Virchows triad.
Treat underlying disorder if known
Corticosteroids for both AAS and autoimmune
disease together
Patients with episodes of thrombosis need
lifelong anticoagulation
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ASA alone is inadequate
LMWHs – good role for these medicines
Bibliography
 Tintinalli Judith E., Emergency Medicine A
Comprehensive Study Guide 6th Edition.
Chapters 218-219
Questions
 T/F Lupus Anticoagulant is always present in
patients with SLE?
 T/F von Willebrand disease is a disorder of
the extrinsic clotting pathway?
 T/F Definitive treatment of DIC is heparin
followed by coumadin therapy?
 T/F Defiencies of proteins C and S cause
thrombotic disorders?
 T/F This was a fun and interesting chapter?
 F, F, F, T, F