anemia and the bleeding patient november 1, 2005 eli denney d.o
TRANSCRIPT
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. Iron deficiency Thalassemia Anemia of Chronic Disease
Physiologic Reactions to Blood Loss
Acute – Peripheral vasoconstriction and central vasodilatation If blood loss continues – small vessel
dilatation with compensatory decreased PVR, resulting in increased CO.
Chronic - Increased plasma volume keeps intravascular volume normal Erythropoietin released by kidneys –
reticulocytes in 3-7 days.
Signs and Symptoms
Depend upon Rate of blood loss Amount of blood lost Age Overall Health Comorbid disease states
Signs and Symptoms
Weakness Fatigue Dyspnea
Palpitations Orthostatic
symptoms Lethargy
Physical Exam Findings
+ Orthostatic BP’s Tachycardia Pallor Systolic ejc. murmur
Widened pulse pressure GI bleeding/Uterine
bleeding Altered Mental Status
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 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 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
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 – 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 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. 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 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 TTP HUS DIC
Viral infections – HIV, Varicella, EBV
Drugs – Heparin/Protamine
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 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
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 Uremia DIC SLE ITP Cardiopulmonary
Bypass
Myeloprolifertive disorders
Dysproteinemias Von Willebrands
disease Leukemias
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 plasmin inhibitor will cause a general state of fibrinolysis and increase D-Dimers and fibrin degradation products
Lab
To evaluate coagulation in liver disease the following labs will need to be ordered 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 Petechiae Ecchymoses GI/GU bleeding Wounds/IV sites
DIC Manifestation
Thrombosis 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
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 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 Increased destruction – immune complex
related and HIV medications Decreased synthesis – immune complex
related and HIV medications
HIV Bleeding Disorders
HIV patients commonly have 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 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 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 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 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 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