Bleeding Disorders Flashcards
Bleeding Disorders
Clinically abnormal bleeding Spontaneous or after an inciting event Components of the normal hemostatic response -Blood vessel wall -Platelets -Clotting cascade
Basic Lab Tests
Platelet count -150,000-450,000 platelets/µl is normal Prothrombin time (PT) -Assess the extrinsic and common pathways -VII, X, V, II, I -Monitor warfarin therapy Partial thromboplastin time (PTT) -Assess the intrinsic and common pathways -XII, XI, IX, VIII, X, V, II, I -Monitor heparin therapy
Lab Tests contin
Bleeding time
-Standardized incision is made—time until bleeding stops
-Measures platelet function
-Problems with variability and poor reproducibility
Fibrin split products
-Indicates the cleavage of fibrin or fibrinogen
D-dimers
-Indicates cleavage of cross-linked fibrin
Factor levels
-Measures individual factor activity
Blood Vessel Abnormalities Increased fragility
Scurvy, amyloidosis, chronic glucocorticoid use, inherited connective tissue disorders, infectious and hypersensitivity vasculitides (meningococcemia, infective endocarditis, rickettsia, typhoid, Henoch-Schönlein purpura)
Spontaneous appearance of petechiae and ecchymoses in the skin and mucous membranes
Lab tests are normal in most cases
Blood Vessel Abnormalities Systemic conditions that activate or damage endothelial cells
Converts lining into prothrombotic surface
Paradoxical consumptive coagulopathy
Often leads to severe bleeding
Platelet Deficiency Qualitative
Uremia, aspirin, myeloproliferative disorder, von Willebrand disease
Easy bruising, nosebleeds, excessive bleeding from minor trauma, menorrhagia
PT and PTT are normal
Bleeding time prolonged
Clotting Factor Derangement
PT and/or PTT are prolonged
Bleeding time is normal
Petechiae and bleeding after minor surface trauma is absent
Massive hemorrhage with surgery or dental procedures or severe trauma
Deep tissue hematomas, lower extremity joint hemorrhages (hemarthoses)
Disseminated Intravascular Coagulation (DIC)
Acute, subacute, or chronic thrombohemorrhagic disorder
Secondary complication in a variety of diseases
Systemic activation of coagulation pathways leads to formation of thrombi throughout the microcirculation
Widespread thromboses leads to consumption of platelets and coagulation factors
Activation of fibrinolysis
DIC can cause tissue hypoxia and microinfarcts from the microthrombi
Widespread fibrin deposition within microcirculation
Hemolysis of red cells as they pass through the narrowed vessels (microangiopathic hemolytic anemia)
DIC can cause bleeding from depletion of platelets and coagulation factors (consumptive coagulopathy) and activation of fibrinolysis
Two major mechanisms trigger DIC
Release of tissue factor or thromboplastic substances into the circulation
Widespread endothelial damage
DIC clinical
Acute DIC is usually dominated by bleeding
-Prolonged, copious post-partum bleeding
-Petechiae and ecchymoses on skin
-Severe hemorrhage into GI or urinary tract
May present as shock, acute renal failure, dyspnea, cyanosis, convulsions, and coma
Chronic DIC tends to present with symptoms related to thrombosis
-Typically abnormal clotting is confined to the microcirculation
-May present with minimal symptoms
DIC labs
Thrombocytopenia
Prolonged PT and PTT
Fibrin split products increased
D-dimers present
DIC prognosis
highly variable
Definitive treatment must be directed at cause of the DIC
Supportive treatment of hemostatic problems
Thrombocytopenia
Decreased production or increased destruction of platelets
Risk of bleeding
-20,000-50,000: increased risk of post-traumatic bleeding
-<20,000: risk of spontaneous bleeding
Thrombocytopenia types of bleeding
Small, superficial blood vessels producing petechiae or ecchymoses in skin and mucous membranes
Larger hemorrhages into the CNS are a major hazard with markedly depressed counts
Thrombocytopenia is the most common
hematological manifestation of HIV
Cause is multifactorial
Thrombocytopenia labs
Prolonged bleeding time
Normal PT and PTT
Primary Immune Thrombocytopenic Purpura
Acute & chronic
Acute Immune Thrombocytopenic Purpura
Affects children
Subsequent to viral infections; self-limited
Chronic Immune Thrombocytopenic Purpura
Affects females 20-40 years of age
80% have antiplatelet antibodies directed against membrane glycoproteins IIb/IIIa or Ib/IX complexes
Spleen is a major site of antibody production and platelet destruction
Splenectomy induces complete remission in 2/3 of patients
Immune Thrombocytopenic Purpura Clinical
Onset of chronic ITP is insidious
Petechiae, easy bruising, epistaxis, gum bleeding, bleeding after minor trauma
Intracerebral and subarachnoid hemorrhages are much less common
Immune Thrombocytopenic Purpura labs
Thrombocytopenia
Marrow exam
? antiplatelet antibodies
Heparin-Induced Thrombocytopenia
Special drug induced thrombocytopenia
3-5% of patients being treated with unfractionated heparin develop a moderate to severe thrombocytopenia after 1-2 weeks of therapy
IgG that binds platelet factor IV on platelet surfaces in a heparin dependant fashion
Heparin-Induced Thrombocytopenia
Activates platelets, induces aggregation and causes thrombosis
Arterial and venous thromboses occur even with marked thrombocytopenia
Can cause severe morbidity and death
Stop all heparin
-Breaks cycle of activation and platelet consumption
-Can recur on subsequent exposure
Thrombotic Thrombocytopenic Purpura (TTP) pentad
Fever, thrombocytopenia, microangiopathic hemolytic anemia, transient neurological deficits, renal failure
Hemolytic-Uremic Syndrome (HUS)
Thrombocytopenia, microangiopathic hemolytic anemia, acute renal failure, affects children
Usually no neurological deficits or fever
Thrombotic Thrombocytopenic Purpura (TTP) and Hemolytic-Uremic Syndrome (HUS) Widespread formation of hyaline thrombi in the microcirculation
Composed of dense aggregates of platelets surrounded by fibrin
Consumption of platelets causes thrombocytopenia
Vessels narrowed by platelet-rich thrombi cause microangiopathic hemolytic anemia
TTP
TTP is treated by plasma exchange and this is successful about 80% of the time
-Prior to this TTP was almost uniformly fatal
Most cases are due to a deficiency of the metalloprotease ADAMTS13
-Degrades very high molecular weight multimers of vWF
-Very high molecular weight multimers of vWF are thought to promote platelet microaggregation throughout the circulation
TTP
Superposition of endothelial injury initiates clinical TTP
Deficiency of ADAMTS13 activity is most often due to an acquired autoantibody
Must consider TTP in patient with unexplained thrombocytopenia and microangiopathic hemolytic anemia—failure to make an early diagnosis can be fatal
HUS
HUS usually occurs following gastroenteritis due to E. coli O157:H7
-Elaborates a Shiga-like toxin that damages endothelial cells initiating platelet activation and aggregation
Normal presentation is bloody diarrhea from the enteritis followed a few days later by HUS
-With supportive care and plasma exchange recovery is possible
-Irreversible renal damage or death are possible in severe cases
Prognosis is worse in cases (10%) where there is no preceding infection by a Shiga toxin producing bacteria
DIC vs. TTP/HUS
In DIC activation of coagulation cascade is primary
In TTP/HUS platelet activation and aggregation is primary
PT and PTT are usually normal in TTP/HUS
Microvascular occlusion, microangiopathic hemolytic anemia, and thrombocytopenia are common to DIC and TTP/HUS
Coagulation Factor Disorders
Acquired coagulation factor deficiencies -Typically involve many factors -Vitamin K deficiency *Can cause a severe coagulation defect *-Factors II, VII, IX, and X Parenchymal liver disease *Liver synthesizes most coagulation factors *Removes many activated factors *Complex hemorrhagic diatheses
von Willebrand Disease
vWF facilitates the adhesion of platelets to damaged blood vessel walls
-Also serves as a carrier for factor VIII in the plasma
Ristocetin agglutination test is a bioassay for vWF
-Ristocetin promotes vWF-platelet interaction resulting in platelet agglutination
von Willebrand Disease
Spontaneous bleeding from mucous membranes, excessive bleeding from wounds, menorrhagia
Prolonged bleeding time with normal platelet count
Most cases transmitted in autosomal dominant pattern
Likely the most common inherited bleeding disorder
Compound defect involving platelet function and coagulation factor pathway
-Amounts of factor VIII are only moderately depressed and platelet function defect dominates the clinical picture (Lab: can see prolonged PTT and prolonged bleeding time)
Type I
classic and most common variant
Autosomal dominant
Reduced quantity of circulating vWF
Decreased factor VIII levels; not clinically significant
Type IIA
High molecular weight multimers are not synthesized
HMWM are the most active form
Qualitative deficiency
Type IIB
Abnormal HMWM are synthesized and rapidly removed
Chronic mild thrombocytopenia in some
Type III
Homozygous form
Very low vWF and factor VIII; resembles hemophilia
Factor VIII Deficiency (Hemophilia A)
X-linked recessive disorder -30% of cases are new mutations Caused by reduction in factor VIII activity Types -Severe: 5% activity
Factor VIII Deficiency (Hemophilia A) clinical
In symptomatic cases, easy bruising and massive hemorrhage after trauma and operative procedures
Spontaneous hemorrhages in areas of body normally subject to trauma
-Especially joints
*Recurrent joint bleeds lead to deformities
-Deep tissue hematomas
-Petechiae are characteristically absent
Factor VIII Deficiency (Hemophilia A) labs
Prolonged PTT
PTT corrects by mixing the patient’s plasma with normal plasma
Factor VIII Deficiency (Hemophilia A)
Treat by factor VIII infusions Some (15%) patients develop neutralizing antibodies against factor VIII -Usually most severely affected patients -Complicates replacement therapy -PTT does not correct with mixing
Factor IX Deficiency (Hemophilia B, Christmas Disease)
X-linked disorder Clinically indistinguishable from hemophilia A PTT prolonged Bleeding time normal Treat by infusion of factor IX
