RBCs and Bleeding Disorders

RBCs and Bleeding RBCs and Bleeding DisordersDisorders

AnemiasAnemias Anemias of blood lossAnemias of blood loss

– Acute blood lossAcute blood loss– Chronic blood lossChronic blood loss

Hemolytic anemiasHemolytic anemias– Hereditary spherocytosis (HS)Hereditary spherocytosis (HS)– Hemolytic disease due to red cell enzyme defects: Glucose-6-Hemolytic disease due to red cell enzyme defects: Glucose-6-

phosphate dehydrogenase deficiencyphosphate dehydrogenase deficiency– Sickle cell diseaseSickle cell disease– Thalassemia syndromesThalassemia syndromes– Paroxysmal nocturnal hemoglobinuriaParoxysmal nocturnal hemoglobinuria– Immunohemolytic anemiaImmunohemolytic anemia– Hemolytic anemia resulting from trauma to red cells – cardiac Hemolytic anemia resulting from trauma to red cells – cardiac

valve prostheses, microangiopathic disordersvalve prostheses, microangiopathic disorders Anemias of diminished erythropoiesisAnemias of diminished erythropoiesis

AnemiasAnemias

Anemia = A reduction of the total circulating red Anemia = A reduction of the total circulating red cell mass below normal limits, reduces the cell mass below normal limits, reduces the oxygen-carrying capacity of the blood, leading to oxygen-carrying capacity of the blood, leading to tissues hypoxiatissues hypoxia

In practice, usually diagnosed based on a In practice, usually diagnosed based on a reduction in H/H, correlate with RBC mass, reduction in H/H, correlate with RBC mass, except when changes in plasma volume caused except when changes in plasma volume caused by fluid retention or dehydrationby fluid retention or dehydration

RBC indices, Table 14-2, adult reference rangesRBC indices, Table 14-2, adult reference ranges Clinical – pale, weakness, malaise, fatigue, DOEClinical – pale, weakness, malaise, fatigue, DOE

Anemia of Blood LossAnemia of Blood Loss

Acute blood loss – mainly effects due Acute blood loss – mainly effects due to to loss of intravascular volumeloss of intravascular volume

Significant bleeding – predictable Significant bleeding – predictable changes changes in the blood involving in the blood involving WBCs and WBCs and platelets as well as RBCsplatelets as well as RBCs

Chronic blood loss – anemia only if rate Chronic blood loss – anemia only if rate of of loss exceeds the regenerative loss exceeds the regenerative capacity capacity of the marrow or iron of the marrow or iron stores are stores are depleteddepleted

Hemolytic AnemiasHemolytic Anemias

Premature destruction of red cells and a Premature destruction of red cells and a shortened red cell life span below shortened red cell life span below

the the normal 120 daysnormal 120 days Elevated erythropoietin levels and a Elevated erythropoietin levels and a

compensatory increase in compensatory increase in erythropoiesiserythropoiesis Accumulation of hemoglobin Accumulation of hemoglobin

degradation products released by red degradation products released by red cell breakdown derived from hemoglobincell breakdown derived from hemoglobin


Extravascular hemolysisExtravascular hemolysis– Premature destruction also occurs in Premature destruction also occurs in

phagocytesphagocytes– Hyperplasia of phagocytes leading to Hyperplasia of phagocytes leading to

splenomegalysplenomegaly– Generally caused by alterations in RBCs Generally caused by alterations in RBCs

that make them less deformablethat make them less deformable– Principal clinical features – anemia, Principal clinical features – anemia,

splenomegaly, jaundice, often benefit from splenomegaly, jaundice, often benefit from splenectomy, decreased haptoglobinsplenectomy, decreased haptoglobin


Intravascular hemolysisIntravascular hemolysis– Caused by mechanical injury, Caused by mechanical injury,

complement fixation, intracellular complement fixation, intracellular parasites, or exogenous toxic factorsparasites, or exogenous toxic factors

– Clinical – anemia, hemoglobinemia, Clinical – anemia, hemoglobinemia, hemoglobinuria, hemosiderinuria, hemoglobinuria, hemosiderinuria, jaundice, no splenomegalyjaundice, no splenomegaly

Hereditary SpherocytosisHereditary Spherocytosis

Intrinsic defects in the red cell membrane Intrinsic defects in the red cell membrane skeleton that render red cells, spheroid, less skeleton that render red cells, spheroid, less deformable, and vulnerable to splenic deformable, and vulnerable to splenic sequestration and destructionsequestration and destruction

Diverse mutations lead to an insufficiency of Diverse mutations lead to an insufficiency of membrane skeletal componentsmembrane skeletal components

Compound heterozygosityCompound heterozygosity Deficiency of membrane skeleton reduces the Deficiency of membrane skeleton reduces the

stability of the lipid bilayer, leading to the loss stability of the lipid bilayer, leading to the loss of membrane fragments as red cells age in of membrane fragments as red cells age in circulationcirculation

Hereditary SpherocytosisHereditary Spherocytosis

Spleen has a cardinal role in the Spleen has a cardinal role in the premature demise of spherocytes, trapped premature demise of spherocytes, trapped in splenic cords and phagocytized, in splenic cords and phagocytized, erthyrostasis leading to decreased glucose erthyrostasis leading to decreased glucose and pHand pH

Increased MCHC due to dehydration Increased MCHC due to dehydration because of loss of K+ and H2Obecause of loss of K+ and H2O

Anemia, Splenomegaly, jaundice, gall Anemia, Splenomegaly, jaundice, gall stones, aplastic crises, hemolytic crises, stones, aplastic crises, hemolytic crises, splenectomy is beneficialsplenectomy is beneficial

Glucose-6-phosphate Glucose-6-phosphate Dehydrogenase DeficiencyDehydrogenase Deficiency

Abnormalities in the hexose monophosphate Abnormalities in the hexose monophosphate shunt or glutathione metabolism resulting from shunt or glutathione metabolism resulting from deficient or impaired enzyme function reduce the deficient or impaired enzyme function reduce the ability of red cells to protect themselves from ability of red cells to protect themselves from oxidative injuries and leads to hemolysisoxidative injuries and leads to hemolysis

G6PD deficiency is a recessive X-linked trait, G6PD deficiency is a recessive X-linked trait, G6PD- and G6PD Mediterranean cause most of G6PD- and G6PD Mediterranean cause most of clinically significant anemiasclinically significant anemias

Episodic hemolysis is characteristic caused by Episodic hemolysis is characteristic caused by exposures that generate oxidant stress, exposures that generate oxidant stress, infections, drugs, foods (e.g. fava beans, infections, drugs, foods (e.g. fava beans, antimalarials)antimalarials)

G6PD DeficiencyG6PD Deficiency

Heinz bodies removed by spleen , Heinz bodies removed by spleen , bite cells in peripheral smearbite cells in peripheral smear

Both intravascular and extravascular Both intravascular and extravascular hemolysishemolysis

Anemia, hemoglobinemia, Anemia, hemoglobinemia, hemoglobinuriahemoglobinuria

Self-limited usuallySelf-limited usually

Sickle Cell diseaseSickle Cell disease

Common hereditary hemoglobinopathy Common hereditary hemoglobinopathy that occurs primarily in individuals of that occurs primarily in individuals of African descent, 8-10% of African African descent, 8-10% of African Americans have HbS trait Americans have HbS trait (heterozygotes)(heterozygotes)

Point mutation in the 6Point mutation in the 6thth codon of Beta- codon of Beta-globin that leads to replacement of globin that leads to replacement of glutamate with valine leading to the HbS glutamate with valine leading to the HbS molecule undergoing polymerization molecule undergoing polymerization when deoxygenated, sickle shapewhen deoxygenated, sickle shape

Sickle Cell DiseaseSickle Cell Disease

Chronic hemolysis, microvascular Chronic hemolysis, microvascular occlusions, tissue damageocclusions, tissue damage

Variables affecting the rate and degree Variables affecting the rate and degree of sicklingof sickling– Interaction of HbS with other types of Interaction of HbS with other types of

hemoglobin in the cellhemoglobin in the cell– MCHC MCHC – Intracellular pHIntracellular pH– Transit time of red cells through the Transit time of red cells through the

microvascular bedsmicrovascular beds


Peripheral blood – variable numbers Peripheral blood – variable numbers of irreversibly sickled cells, of irreversibly sickled cells, reticulocytosis, target cell, Howell-reticulocytosis, target cell, Howell-Jolly bodies, pigment gallstones, Jolly bodies, pigment gallstones, hyperbilirubinemia, hyperbilirubinemia, autosplenectomy, infarctions in autosplenectomy, infarctions in many tissuesmany tissues


Increased susceptibility to infectionsIncreased susceptibility to infections CrisesCrises

– Vaso-oclusive =pain crisesVaso-oclusive =pain crises– Acute chest syndromeAcute chest syndrome– Sequestration crisesSequestration crises– Aplastic crisesAplastic crises

Thalassemia SyndromesThalassemia Syndromes

Heterogenous group of disorders Heterogenous group of disorders caused by inherited mutations that caused by inherited mutations that decrease the synthesis of adult decrease the synthesis of adult hemoglobin, HbAhemoglobin, HbA

Alpha-globin genes on chromosome 16Alpha-globin genes on chromosome 16 Beta-globin gene on chromosome 11Beta-globin gene on chromosome 11 Table 14-3 – clinical and genetic Table 14-3 – clinical and genetic

classification of thalassemias classification of thalassemias

Beta-ThalassemiasBeta-Thalassemias

Mutations that diminish the synthesis Mutations that diminish the synthesis of beta-globin chainsof beta-globin chains– BetaBeta00 mutations – absent beta-globin mutations – absent beta-globin

synthesissynthesis Chain terminator mutationsChain terminator mutations

– BetaBeta++ mutations – reduced beta-globin mutations – reduced beta-globin synthesissynthesis

Splicing mutationsSplicing mutations Promoter region mutationsPromoter region mutations


Two mechanisms leading to anemiaTwo mechanisms leading to anemia– Hypochromic, microcytic anemia with Hypochromic, microcytic anemia with

decreased oxygen transport capacitydecreased oxygen transport capacity– Diminished survival of red cells and Diminished survival of red cells and

precursorsprecursors Membrane damageMembrane damage Ineffective erythropoiesisIneffective erythropoiesis Extravascular hemolysisExtravascular hemolysis Extramedullary hematopoiesisExtramedullary hematopoiesis Excessive absorption of ironExcessive absorption of iron


Clinical syndromesClinical syndromes– Beta-thalassemia majorBeta-thalassemia major– Beta-thalassemia minor or traitBeta-thalassemia minor or trait– Beta-thalassemia intermediaBeta-thalassemia intermedia

Alpha-ThalassemiasAlpha-Thalassemias

Inherited deletions that result in reduced or Inherited deletions that result in reduced or absent synthesis of alpha-globin chainsabsent synthesis of alpha-globin chains

Clinical syndromes – determined and classified by Clinical syndromes – determined and classified by the number of alpha-globin genes that are the number of alpha-globin genes that are deleteddeleted– Silent carrier – deletion of one geneSilent carrier – deletion of one gene– Alpha-thalassemia trait – deletion of two genesAlpha-thalassemia trait – deletion of two genes– Hemoglobin H disease – deletion of three Hemoglobin H disease – deletion of three

genesgenes– Hydrops fetalis – deletion of all four genesHydrops fetalis – deletion of all four genes

Paroxysmal Nocturnal Paroxysmal Nocturnal HemoglobinuriaHemoglobinuria

Acquired mutations in the phosphatidylinositol Acquired mutations in the phosphatidylinositol glycan complementation group A gene ( PIGA), glycan complementation group A gene ( PIGA), an enzyme that is essential for the synthesis of an enzyme that is essential for the synthesis of certain cell surface proteinscertain cell surface proteins

Intravascular hemolysis caused by the C5b-C9 Intravascular hemolysis caused by the C5b-C9 membrane attack complexmembrane attack complex

Thrombosis is the leading cause of disease-Thrombosis is the leading cause of disease-related death because of dysfunction of related death because of dysfunction of plateletsplatelets

5-10% develop AML or myelodysplastic 5-10% develop AML or myelodysplastic syndromessyndromes

Immunohemolytic AnemiaImmunohemolytic Anemia

Caused by antibodies that bind to red Caused by antibodies that bind to red cells, leading to their premature cells, leading to their premature destructiondestruction

Direct Coombs antiglobulin testDirect Coombs antiglobulin test Indirect Coombs antiglobulin testIndirect Coombs antiglobulin test Table 14-4 ClassificationTable 14-4 Classification

– Warm Antibody typeWarm Antibody type– Cold agglutinin typeCold agglutinin type– Cold hemolysin typeCold hemolysin type

Anemias of Diminshed Anemias of Diminshed ErythropoiesisErythropoiesis

Megaloblastic anemiasMegaloblastic anemias Iron deficiency anemiaIron deficiency anemia Anemia of chronic diseaseAnemia of chronic disease Aplastic anemiaAplastic anemia Pure red cell aplasiaPure red cell aplasia Other forms of marrow failureOther forms of marrow failure

Megaloblastic AnemiasMegaloblastic Anemias

Caused by an impairment of DNA Caused by an impairment of DNA synthesis that leads to distinctive synthesis that leads to distinctive morphologic changes, including morphologic changes, including abnormally large erythroid precursors and abnormally large erythroid precursors and red cellsred cells

Table 14-5 Causes of megaloblastic Table 14-5 Causes of megaloblastic anemiasanemias

Macrocytic oval cells, hypersegmented Macrocytic oval cells, hypersegmented neutrophils, giant metamyelocytes and neutrophils, giant metamyelocytes and band formsband forms

Vitamin B12 DeficiencyVitamin B12 Deficiency

Pernicious anemiaPernicious anemia– Autoimmune gastritis leading to failure Autoimmune gastritis leading to failure

of intrinsic factor production leading to of intrinsic factor production leading to vitamin B12 deficiencyvitamin B12 deficiency

– Atrophy of the fundic glands, Atrophy of the fundic glands, intestinalization, atrophic glossitis, CNS intestinalization, atrophic glossitis, CNS – demyelination of the dorsal and lateral – demyelination of the dorsal and lateral tracts leading to spastic paraparesis, tracts leading to spastic paraparesis, sensory ataxia, severe paresthesias in sensory ataxia, severe paresthesias in the lower limbs the lower limbs

Folate DeficiencyFolate Deficiency

Three major causesThree major causes– Decreased intake – chronic alcoholics, Decreased intake – chronic alcoholics,

elderly, indigentelderly, indigent– Increased requirements – pregnancy, Increased requirements – pregnancy,

infancyinfancy– Impaired utilization – folic acid Impaired utilization – folic acid

antagonistsantagonists

Iron Deficiency anemiaIron Deficiency anemia

Most common nutritional disorder in the Most common nutritional disorder in the worldworld

Iron in the body is recycled extensively Iron in the body is recycled extensively between the functional and storage poolsbetween the functional and storage pools– TransferrinTransferrin– FerritinFerritin

Iron balance is maintained largely by Iron balance is maintained largely by regulating the absorption of dietary iron in regulating the absorption of dietary iron in the proximal duodenum, hepcidinthe proximal duodenum, hepcidin

Iron DeficiencyIron Deficiency

CausesCauses– Dietary lackDietary lack

Infants, impoverished,elderly, teenagersInfants, impoverished,elderly, teenagers

– Impaired absorptionImpaired absorption– Increased requirementsIncreased requirements– Chronic blood loss-most common cause Chronic blood loss-most common cause

in the Western world – GI bleed until in the Western world – GI bleed until proven otherwiseproven otherwise

Iron DeficiencyIron Deficiency

Hypochromic, microcytic anemiaHypochromic, microcytic anemia Low serum iron and ferritinLow serum iron and ferritin Elevated TIBCElevated TIBC Disappearance of stainable iron in Disappearance of stainable iron in

the macrophages of the bone the macrophages of the bone marrowmarrow

Anemia of Chronic DiseaseAnemia of Chronic Disease

Chronic microbial infections, such as Chronic microbial infections, such as osteomyelitis, endocarditis, lung osteomyelitis, endocarditis, lung abscessabscess

Chronic immune disorders, such as RAChronic immune disorders, such as RA Neoplasms, lung and breast, non-Neoplasms, lung and breast, non-

Hodgkin lymphomasHodgkin lymphomas Iron sequestrationIron sequestration Increase iron in marrow macrophages, Increase iron in marrow macrophages,

high ferritin, decreased TIBChigh ferritin, decreased TIBC

Aplastic AnemiasAplastic Anemias

Chronic primary hematopoietic failure and Chronic primary hematopoietic failure and attendant pancytopeniaattendant pancytopenia

Major causes – table 14-7Major causes – table 14-7 Most common known etiology drugs and Most common known etiology drugs and

chemicals also infections, whole body chemicals also infections, whole body irradiation, Fanconi anemiairradiation, Fanconi anemia

Pure red cell aplasiaPure red cell aplasia Other forms – myelophthisic anemia, chronic Other forms – myelophthisic anemia, chronic

renal failure, hepatocellular liver disease, renal failure, hepatocellular liver disease, endocrine disorders ( hypothyroidism)endocrine disorders ( hypothyroidism)

PolycythemiasPolycythemias

Table 14-8Table 14-8

Bleeding DisordersBleeding Disorders

Increased fragility of the vesselsIncreased fragility of the vessels

Platelet deficiency or dysfunctionPlatelet deficiency or dysfunction

Derangement of coagulationDerangement of coagulation

Disorder Bleedingtime

Platelet Count

PT PTT ThrombinTimeFibrinogenAssay

Con-firmatoryTesting

VascularBleeding

Usually prolong-ed

Normal Normal Normal Normal

Throm-bocyto-penia

Pro-longed

De-creased

Normal Normal Normal

Qualita-tive Platelet Defects

Pro-longed

Normal Normal Normal Normal PlateletAggre-gation/special studies

Classic Hemo-philia

Normal Normal Normal Pro-longed

Normal FactorVIIIAssay

Christ-mas Disease

Normal Normal NormalPro-longed

Normal Factor IX Assay

Von Wille-brand Disease

Pro-longed

Normal Normal Pro-longed

Normal vWF assay

DIC Pro-longed

De-creased

Pro-longed

Pro-longed

Pro-longed

Fibrin and FDP

Laboratory Screening Tests in Selected Hemorrhagic Disorders

Coagulation CascadeCoagulation Cascade PTT PT PTT PT

Coagulation CascadeCoagulation Cascade

www.hopkinsmedicine.org/www.hopkinsmedicine.org/hematology/coagulation.swfhematology/coagulation.swf

Bleeding Disorders: Bleeding Disorders: Hemorrhagic DiathesesHemorrhagic Diatheses

Bleeding disorders caused by vessel wall abnormalitiesBleeding disorders caused by vessel wall abnormalities Bleeding related to platelet number: thrombocytopeniaBleeding related to platelet number: thrombocytopenia

– Chronic immune thrombocytopenia purpuraChronic immune thrombocytopenia purpura– Acute immune thrombocytopenia purpuraAcute immune thrombocytopenia purpura– Drug-induced thrombocytopeniaDrug-induced thrombocytopenia– HIV-associated thrombocytopeniaHIV-associated thrombocytopenia– Thrombotic microangiopathiesThrombotic microangiopathies

Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremia Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremia syndrome (HUS)syndrome (HUS)

Bleeding disorders related to defective platelet functionsBleeding disorders related to defective platelet functions Hemorrhagic Diatheses related to abnormalities in clotting factorsHemorrhagic Diatheses related to abnormalities in clotting factors

– The factor VIII-vWF complexThe factor VIII-vWF complex– Von Willebrand diseaseVon Willebrand disease– Hemophilia A (factor VIII deficiency)Hemophilia A (factor VIII deficiency)– Hemophilia B (Christmas disease, Factor IX deficiencyHemophilia B (Christmas disease, Factor IX deficiency

Disseminated intravascular coagulationDisseminated intravascular coagulation

Vessel Wall AbnormalitiesVessel Wall Abnormalities

Infections (e.g. meningococcemia)Infections (e.g. meningococcemia) Drug reactionsDrug reactions Scurvy, Ehlers-Danlos, CushingScurvy, Ehlers-Danlos, Cushing HSPHSP Hereditary hemorrhagic Hereditary hemorrhagic

telangiestasia (Weber-Osler-Rendu)telangiestasia (Weber-Osler-Rendu) Perivascular amyloidosisPerivascular amyloidosis

ThrombocytopeniaThrombocytopenia

Count <20,000 = spontaneous bleedingCount <20,000 = spontaneous bleeding Decreased production = bone marrow Decreased production = bone marrow

issueissue Decreased platelet survival = Decreased platelet survival =

immunologic immunologic or nonimmunologicor nonimmunologic Sequestration = hypersplenismSequestration = hypersplenism Dilution = transfusionsDilution = transfusions Table 14-9 Causes of ThrombocytopeniaTable 14-9 Causes of Thrombocytopenia

Chronic Immune Chronic Immune Thrombocytopenic Purpura ( ITP)Thrombocytopenic Purpura ( ITP)

Cause – autoantibodies to platelets act as Cause – autoantibodies to platelets act as opsonins, primary (diagnosis of exclusion) or opsonins, primary (diagnosis of exclusion) or secondary ( e.g SLE, HIV, B-cell neoplasms)secondary ( e.g SLE, HIV, B-cell neoplasms)

Spenectomy helps – site of removal of Spenectomy helps – site of removal of opsonized platelets, site of plasma cells that opsonized platelets, site of plasma cells that produce autoantibodiesproduce autoantibodies

Megakaryocytes – increased number and size Megakaryocytes – increased number and size in marrowin marrow

Most common – women over 40 years of age, Most common – women over 40 years of age, petechiae, echymoses, risk of intracranial petechiae, echymoses, risk of intracranial bleedsbleeds

Other Causes of Other Causes of ThrombocytopeniaThrombocytopenia

Acute ITP – children, following a viral Acute ITP – children, following a viral illness, usually self-limitedillness, usually self-limited

Drug-induced – heparin-induced Drug-induced – heparin-induced (HIT)-severe form – thrombosis, even (HIT)-severe form – thrombosis, even in setting of low plateletsin setting of low platelets

HIV-associated – megakarocytes HIV-associated – megakarocytes infectedinfected

Thrombotic Thrombotic MicroangiopathiesMicroangiopathies

Caused by insults that lead to Caused by insults that lead to excessive activation of platelets, which excessive activation of platelets, which deposit as thrombi in microcirculatory deposit as thrombi in microcirculatory beds – microangiopathic hemolytic beds – microangiopathic hemolytic anemia, organ dysfunction, anemia, organ dysfunction, thrombocytopenia – Table 14-10thrombocytopenia – Table 14-10

Thrombotic thrombocytopenic purpura Thrombotic thrombocytopenic purpura (TTP)(TTP)

Hemolytic-uremic syndrome (HUS)Hemolytic-uremic syndrome (HUS)

Defective Platelet Defective Platelet DysfunctionsDysfunctions

Defects of adhesion – Bernard-Soulier syndrome – Defects of adhesion – Bernard-Soulier syndrome – inherited deficiency of platelet membrane inherited deficiency of platelet membrane glycoprotein complex (receptor for vWF)glycoprotein complex (receptor for vWF)

Defective platelet aggregation – Glanzmann Defective platelet aggregation – Glanzmann thrombasthenia – AR - deficiency or dysfunction thrombasthenia – AR - deficiency or dysfunction of glycoprotein Iib-IIIa (integrin that participates of glycoprotein Iib-IIIa (integrin that participates in “bridge formation” between platelets)in “bridge formation” between platelets)

Defects of platelet secretion – storage pool Defects of platelet secretion – storage pool disordersdisorders

Acquired – aspirin and other NSAIDs, uremiaAcquired – aspirin and other NSAIDs, uremia

Abnormalities in Clotting Abnormalities in Clotting FactorsFactors

Most commonly manifest as large post-Most commonly manifest as large post-traumatic ecchymoses or hematomas traumatic ecchymoses or hematomas or prolonged bleeding after a or prolonged bleeding after a laceration or surgical procedurelaceration or surgical procedure

Hereditary – usually single clotting Hereditary – usually single clotting factorfactor

Acquired – usually multiple factors Acquired – usually multiple factors simultaneously (e.g. vitamin K simultaneously (e.g. vitamin K deficiency)deficiency)

Von Willebrand DiseaseVon Willebrand Disease Most common inherited bleeding disorder of Most common inherited bleeding disorder of

humans ( 1% of adults in US)humans ( 1% of adults in US) 20 variants20 variants Type 1 and Type 3 are associated with a reduced Type 1 and Type 3 are associated with a reduced

quantity of circulating vWFquantity of circulating vWF Type 2 is characterized by qualitative defects in Type 2 is characterized by qualitative defects in

vWFvWF Defects in platelet function despite a normal Defects in platelet function despite a normal

platelet count leading to secondary abnormalties in platelet count leading to secondary abnormalties in platelet adhesion and clot formationplatelet adhesion and clot formation

Clinically – Epistaxis, excessive bleeding from Clinically – Epistaxis, excessive bleeding from wounds, menorrhagiawounds, menorrhagia

Hemophilia A (Factor VIII Hemophilia A (Factor VIII Deficiency)Deficiency)

Most common hereditary disease Most common hereditary disease associated with life-threatening associated with life-threatening bleedingbleeding

X-linked recessiveX-linked recessive Clinical severity correlates well with Clinical severity correlates well with

level of factor VIII activitylevel of factor VIII activity Petechiae are characteristically absentPetechiae are characteristically absent Prolonged PTT, normal PTProlonged PTT, normal PT

Hemophilia B (Christmas Hemophilia B (Christmas Disease, Factor IX Disease, Factor IX

Deficiency)Deficiency) Clinically indistinguishable from Clinically indistinguishable from

hemophilia A – factors VIII and IX hemophilia A – factors VIII and IX function together to activate factor Xfunction together to activate factor X

Disseminated Intravascular Disseminated Intravascular Coagulation (DIC)Coagulation (DIC)

Acute, subacute, or chronic Acute, subacute, or chronic thrombohemorrhagic disorder thrombohemorrhagic disorder characterized by the excessive activation characterized by the excessive activation of coagulation, which leads to the of coagulation, which leads to the formation of thrombi in the formation of thrombi in the microvasculature of the bodymicrovasculature of the body

Consumption of platelets, fibrin, and Consumption of platelets, fibrin, and coagulation factors and activation of coagulation factors and activation of fibrinolysisfibrinolysis

Not a primary diseaseNot a primary disease

DICDIC Two major mechanisms trigger DIC - Table 14-27Two major mechanisms trigger DIC - Table 14-27

– Release of tissue factor or thromboplastic substances into the circulationRelease of tissue factor or thromboplastic substances into the circulation– Widespread injury to endothelial cellsWidespread injury to endothelial cells

Most likely associated with:Most likely associated with:– Obstetric complicationsObstetric complications– Malignant neoplasmsMalignant neoplasms– Sepsis Sepsis – Major traumaMajor trauma

Possible consequencesPossible consequences– Widespread deposition of fibrin – ischemia, microangiopathic hemolytic anemiaWidespread deposition of fibrin – ischemia, microangiopathic hemolytic anemia– Hemorrhagic diathesis Hemorrhagic diathesis

Clinical FeaturesClinical Features– Microangiopathic hemolytic anemiaMicroangiopathic hemolytic anemia– Dyspnea, cyanosis, respiratory failureDyspnea, cyanosis, respiratory failure– Convulsions and comaConvulsions and coma– Oliguria and renal failureOliguria and renal failure– ShockShock– Only definitive treatment is to remove or treat the inciting causeOnly definitive treatment is to remove or treat the inciting cause

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RBCs and Bleeding Disorders