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Flashcards in Bleeding Disorders Deck (43):

Bleeding Disorders

Clinically abnormal bleeding
Spontaneous or after an inciting event
Components of the normal hemostatic response
-Blood vessel wall
-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
-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
-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

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



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

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 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



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 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



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
-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