rbcs and bleeding disorders
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RBCs and Bleeding Disorders. Anemias. Anemias of blood loss Acute blood loss Chronic blood loss Hemolytic anemias Hereditary spherocytosis (HS) Hemolytic disease due to red cell enzyme defects: Glucose-6-phosphate dehydrogenase deficiency Sickle cell disease Thalassemia syndromes - PowerPoint PPT PresentationTRANSCRIPT
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
Hemolytic AnemiasHemolytic Anemias
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
Hemolytic AnemiasHemolytic Anemias
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
Sickle Cell DiseaseSickle Cell Disease
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
Sickle Cell DiseaseSickle Cell Disease
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
Beta-ThalassemiasBeta-Thalassemias
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
Beta-ThalassemiasBeta-Thalassemias
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