Bleeding conditions Flashcards
Platelet Function Assay
● Time it takes to clot a damaged vessel
● Measures platelet adhesion and aggregation
● Whole blood is passed over a membrane containing collagen and epinephrine or ADP
● Reported as the seconds required to close a small aperture in the membrane
● Less invasive, and more reproducible
Prothrombin time assesses function of the ____ and common pathway
extrinsic
Time required for a fibrin clot formation
Prothrombin time
Normally 11-15 seconds
Partial Thromboplastin Time is Used to assess the ____ and Common Pathway
Intrinsic
Prolonged if over 35 sec (normally 25-35 seconds)
Partial Thromboplastin Time
Coagulation Factor Assays (V, VII, VIII, IX, X, XI, XII)
● Used to detect specific coagulation factors
● Used to evaluate blood with abnormal PT and PTT
● Test is done by adding a factor, and watching for correction of the PT and PTT
● Various disease states hereditary or otherwise, contribute to clotting factor deficiencies
disorders of Primary Hemostasis are
those disorders that deal with ____
low platelet count or some
form of platelet dysfunction.
PT and PTT should be normal in disorders of ____ hemostasis
primary
Thrombocytopenia simply means low ____
Platelet count
Thrombocytopenia can be due to either
○ Decreased Platelet production
○ Enhanced Platelet destruction
Pathophysiology of thrombocytopenia - Examples of Decreased Production of Platelets-
■ Bone marrow failure (ex: Aplastic Anemia)
■ Malignant infiltration of the the bone marrow
■ Exposure to some meds, chemotherapy, or radiation
■ Significant nutritional deficiencies
Pathophysiology of thrombocytopenia - Examples of Increased Destruction of Platelets
■ Immune Thrombocytopenia (ex: ITP)
■ Heparin-Induced Thrombocytopenia
■ Disseminated Intravascular Coagulopathy (DIC)
■ Hypersplenism (ex: Related to cirrhosis, lymphoma)
■ Septicemia
Thrombocytopenia Exam and Lab Findings:
○ If significant Thrombocytopenia, Petechiae, Purpura, or
Ecchymosis may develop with little or no explanation.
○ Platelet count will be low on CBC.
____ are flat, red, pinhead-sized lesions
that can appear anywhere on the body
but more likely to be seen in dependent
areas. They do not blanch with pressure.
Petechiae
____ is the coalescence of
petechiae on the surface of the skin.
They are nonpalpable and are more of a
purple color. They also do not blanch.
Dry Purpura
The finding of purpura on mucous
membranes (rather than the skin) is
sometimes referred to as ____
Wet Purpura
This is generally considered to be a sign
for more serious bleeding as platelet
counts are typically very low in order for
wet purpura to occur.
Thrombocytopenia: Treatment and Management
○ Treatment obviously depends on the
underlying condition causing the
Thrombocytopenia.
An acquired autoimmune disorder characterized by isolated
thrombocytopenia, maybe without an apparent cause
ITP
● Immune Thrombocytopenic Purpura (previously called “idiopathic”)
What is this
Wet purpura
Epidemiology of ITP
● Occurs predominantly in young children; peak incidence is between 2 and 5 years of age.
● Can occur in adulthood as well, usually more insidious.
○ Usually between 20-50 years of age
ITP Pathophysiology
○ An antibody is inappropriately produced that binds to surface antigens GPIIb/IIa and others
○ The antibody-coated platelets are then bound by a splenic macrophage and destroyed in the spleen → Shortened half life
■ Thrombocytopenia occurs as a result of accelerated splenic destruction of the platelets.
Primary vs secondary ITP
Primary ITP: Acquired immune thrombocytopenia without an apparent
cause
Secondary ITP: ITP associated with another condition with an inciting event
ITP: Characteristic Signs and Symptoms
bleeding, spontaneous bruising, epistaxis,
gingival, with platelet counts 10,000 - 20,000/mcL
○ Adult women may have menorrhagia.
○ Intracranial hemorrhage is an infrequent occurrence, but it is
the most common cause of death among patients with ITP.
Diagnostic testing for ITP
○ Hallmark is Isolated Thrombocytopenia.
■ If other abnormalities on CBC, likely not ITP
■ If bleeding has occurred, sure, may have anemia
○ PT/INR and PTT are normal.
○ Bone Marrow biopsy may show increased number of Megakaryocytes
ITP Treatment:
○ Avoidance of trauma, NSAIDs, and Aspirin.
○ Childhood ITP is usually self-limited and often does not require treatment.
○ Short course of Steroids is usually the mainstay of treatment
○ Platelet transfusion can be given in severe hemorrhage
○ Relapse can occur, rituximab and TPO mimetics in refractory cases
○ Splenectomy reserved for persistent, chronic cases (risks?)
TTP
Thrombotic Thrombocytopenic Purpura (TTP)
Thrombotic Thrombocytopenic Purpura (TTP)
● Uncommon condition that was mysterious and usually fatal only 15-20 years ago.
○ Can still be acutely life-threatening
● Characterized by Thrombocytopenia, Hemolytic Anemia, and Impairment of Renal function.
○ Considered a Microangiopathic Hemolysis
Pathophysiology of TTP
○ It’s believed the disease occurs due to the
presence of “high molecular weight
multimers of vWF.”
○ The high molecular weight vWF seems to
tether clumps of platelets to endothelial
surfaces sporadically.
Deficiency in the protease ADAMTS13 has
been identified with ___
TTP
Characteristic Signs and Symptoms of TTP
○ Most patients present with fever.
○ Thrombocytopenia
○ Microangiopathic hemolytic anemia
○ Renal impairment
○ Neurologic dysfunction is characteristic of the disease, but not always present.
TTP Additional diagnostic testing:
○ Anemia on CBC
○ Elevated Lactate Dehydrogenase (LDH)
○ Reticulocytosis
○ Schistocytosis
○ Thrombocytopenia
○ Elevated BUN/Creatinine
TTP Treatment and Management
○ Mortality rate is greater than 95% without treatment!
○ Plasma Exchange is the primary treatment.
○ Platelet transfusion is contraindicated as the initial treatment
○ Glucocorticoids and rituximab- immunosuppressive
○ Caplacizumab for high risk- monoclonal binds to vWF
○ Hemodialysis
○ Sometimes blood transfusions are necessary to treat anemia.
○ With plasma exchange, 80-90% recover completely
Hemolytic Uremic Syndrome classic triad
○ Hemolytic Anemia
○ Thrombocytopenia
○ Renal Dysfunction
(just like with TTP)
What differentiates HUS from TTP?
Classically differentiated from TTP by absence of Neurologic symptoms. Although ¼ can get neurologic signs
Hemolytic Uremic Syndrome pathophysiology
○ About 50% of cases are caused by an enteropathic strain of E coli
(O157:H7), which releases a Shiga-like toxin.
○ Primary lesions are of the endothelium of arterioles with formation of platelet thrombi, resulting in thrombosis and
necrosis of the intrarenal vessels. ↑urea in the blood.
Hemolytic Uremic Syndrome Characteristic Signs and Symptoms
○ In young children, a history of recent and/or recurrent
diarrhea is classic for HUS. Often bloody dirrhea
○ Pallor is common.
○ Cutaneous or GI bleeds are possible.
○ Oliguria- Significant kidney injury
○ Abdominal pain
○ Nausea/vomiting
○ Neurologic symptoms are very rare in childhood HUS.
○ HUS in adulthood is a continuum of TTP and neurologic
symptoms are possible
Hemolytic Uremic Syndrome diagnostic testing
○ Hemolytic anemia (less severe than TTP)
○ Thrombocytopenia (less severe than TTP)
○ Acute renal injury (more severe than TTP)
○ Elevated LDH
○ Reticulocytosis
○ Schistocytosis
○ Stool culture may be positive for E coli O157:H7
○ PT/INR and PTT will be normal
Hemolytic Uremic Syndrome Treatment and management
○ Treatment for HUS is primarily supportive.
○ Most children with diarrhea-associated HUS recover within 2-3 weeks.
○ In severe cases, blood transfusions,
○ Eculizumab- Monoclonal antibodies when severe
○ Early hemodialysis improves outcome.
von Willebrand’s Disease inheritence
Autosomal Dominant disorder that results from deficient or defective vWF and causes ineffective platelet adhesion.
○ von Willebrand’s Disease is the most common inherited bleeding disorder.
von Willebrand’s Disease Pathophysiology
○ Normal vWF serves two main functions-
■ Molecule that adheres platelet to injured endothelium
■ Chaperone to Factor VIII, slowing its degradation
Several types of vWD
■ Type 1 (75-80% of vWD): Common, Low levels of vWF
● vWF levels are perhaps 15-60% of normal
■ Type 2 (20-22%): Several subtypes
● vWF levels are normal, but vWF is defective
■ Type 3 (rare): Homozygous, very low levels of vWF
● vWF levels are less than 5% of normal, big concern for bleeding
von Willebrand’s Disease Characteristic Signs and Symptoms
○ If there is bleeding, it is most commonly mild to moderate integument or mucosal bleeding
○ Common history is bleeding more than normal in childhood/teenager after surgery or trauma with parents reporting a similar problem when they were young.
○ Severe bleeding is less common- Type 2 vWD usually has moderate to severe bleeding in childhood.
von Willebrand’s Disease Diagnostic Testing:
○ Platelet count is normal; they are there and functioning.
○ Aggregation studies (Platelet Function assays) are normal except for Ristocetin assay
○ vWF levels are generally measured as low, esp Type 3.
○ Factor VIII levels are generally low as well.
von Willebrand’s Disease Treatment and Management
○ Aspirin can significantly affect vWD patients.
■ Avoid Aspirin!
○ Most cases require no treatment unless having surgery.
○ Intranasal DDAVP (Desmopressin) can be given 30-90 minutes prior to surgery (Best for type 1).
■ Can be given after dental procedures (etc.) if oozing is occuring.
■ DDAVP causes release of vWF and Factor VIII from storage sites
(increasing vWF 2-7 fold).
○ In cases of significant bleeding (Type 3 usually), IV Humate-P (vWF/Factor VIII concentrate) can be given.
disorders of Secondary
Hemostasis are those that deal with ____
Factor deficiencies or dysfunctions within the Coagulation Cascade
Disorders of Secondary Hemostasis include
○ Hemophilia A
○ Hemophilia B
○ Liver Disease-Induced
○ Vitamin K Deficiency
Hemophilia A
Hemophilia A is hereditary bleeding
disorder that is considered X-Linked
Recessive.
___ is the most common severe bleeding disorder
Hemophilia A
Hemophilia A Pathophysiology
○ The disorder leads to a deficiency in
Coagulation Factor VIII.
○ Factor IX is unable to activate Factor
X, so coagulation is dysfunctional
.
Hemophilia A Characteristic Signs and Symptoms
○ Bleeds in deep tissue is characteristic.
○ Spontaneous Hemarthroses- Essentially diagnostic!
○ Can also bleed into muscles, GI tract, and base of tongue
What is this called and indicative of?
Spontaneous Hemarthroses- Essentially diagnostic for hemophilia A
Hemophilia A Diagnostic Testing
○ Because the Intrinsic Pathway is completely dependant
on Factor VIII, PTT is prolonged with Hemophilia A.
○ Coagulation Factor VIII Assay will show decreased levels.
Hemophilia A Treatment and Management
○ Repeated hemarthrosis may lead to joint deformities.
○ Patients with Hemophilia should avoid any contact sports, Aspirin, and IM injections.
○ Recommended treatment is…
■ IV infusion of Factor VIII concentrate.
■ Severe cases get 2-3 x / wk prophylactically
■ Emicizumab- prophylaxis X→Xa
○ DDAVP may also be administered (no more than once every 48 hours)
Hemophilia B differences from A
● Essentially the exact same disease as Hemophilia A, only a few specific differences.
● This X-Linked Recessive disorder is less common and is a deficiency of Factor IX
● Labs are the same, except it is Factor IX decreased on assay
“Christmas Disease”
Hemophilia B
Hemophilia B Treatment and Management
○ Factor IX concentrate is mainstay of treatment-
■ Most Factor IX concentrates also contain Factors II, VII, and X.
● Creates an increased risk of clotting when receiving treatment.
○ DDAVP is not used for Hemophilia B.
○ Otherwise, treatment and recommendations are the same for Hemophilia A and B
Vitamin K Deficiency pathophysiology
Vitamin K deficiency bleeding disorder can be caused by…
■ Warfarin therapy
■ Poor diet
■ Malabsorption
● Antibiotic-related diarrhea
● Inflammatory bowel disease
■ Biliary obstruction
Vitamin K Deficiency Diagnostic Testing
○ PT/INR and PTT are elevated.
■ PT is generally more affected than PTT (but both really)
○ Platelet level is generally normal.
○ Platelet function studies would be normal
Vitamin K Deficiency treatment
○ Treatment depends on the etiology.
○ If poor diet or malabsorption problem, fix it.
○ If on Warfarin and PT/INR is too high, decrease dose.
○ If acute bleeding due to Vitamin K deficiency…
■ Vitamin K replacement (IV or PO; SQ is less predictable)
■ Administration of FFP may be indicated in emergencies
The liver is responsible for
production of all coagulation
factors except____
VIII and vWF.
Characteristic Signs and Symptoms of Liver Disease-Induced coagulation issues
○ Any type of bleeding is a possible
sign/symptom.
○ Assess for signs of liver failure
(jaundice, caput medusae, ascites, etc)
Diagnostic Testing for Liver Disease-Induced coagulation issues
○ Characteristically shows prolonged PT and PTT.
■ Administration of Vitamin K will not correct this
○ May see Thrombocytopenia secondary to hypersplenism.
Liver Disease-Induced Treatment and Management:
○ Treatment should be focused on optimizing liver function.
○ If in end-stage hepatic failure, treatment is difficult.
■ Transplantation will correct the coagulopathy
HEM-HEMOST-2
○ If there is an acute bleed, FFP can be
administered.
DIC
Disseminated Intravascular Coagulation
Disseminated Intravascular Coagulation
● Uncontrolled activation of coagulation
■ → depletion of clotting factors and fibrinogen
■ Thrombocytopenia as platelets are used up
DIC Pathophysiology
○ The pathophysiology is very complex, but at the core is the extensive release of Tissue Factor.
■ Due to widespread tissue injury or endovascular damage
○ This leads to widespread Coag Cascade ignition in such a way that the coagulation factors are consumed.
● Leading to widespread Fibrin production
○ Platelets are activated and bind to endovascular tissue.
○ The presence of widespread fibrin chunks and microvascular coagulation
results in RBC hemolysis
○ Plasminogen is activated into Plasmin, which breaks down some of the Fibrin, so
degradation products are present
DIC Diagnostic testing
○ Early Dz may show low normals ○ Thrombocytopenia ○ Elevated PT/INR ○ Elevated aPTT ○ Reduced fibrinogen levels ○ Elevated D-Dimer ○ Schistocytes on blood smear ○ Low levels of Coag Factors ○ Commonly see acute renal injury ■ Elevated BUN/Creatinine
○ As you can see, everything is off
DIC Treatment and Management
○ Once DIC sets in, Mortality rates are 50-60%.
○ Most important part of treatment is first treat the underlying disease.
○ Admission to the hospital with hematology consult
HELLP Syndrome can progress to DIC
Hemolysis, Elevated Liver enzymes, Low Platelets
DIC as a complication of pregnancy
● HELLP Syndrome can progress to DIC
● Hemolysis, Elevated Liver enzymes, Low Platelets
● Kidney injury
● High mortality rate
● Treatment includes delivery
