Bleeding conditions

Question 1

Platelet Function Assay

Answer 1

● 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

Question 2

Prothrombin time assesses function of the ____ and common pathway

Answer 2

extrinsic

Question 3

Time required for a fibrin clot formation

Answer 3

Prothrombin time
Normally 11-15 seconds

Question 3

Partial Thromboplastin Time is Used to assess the ____ and Common Pathway

Answer 3

Intrinsic

Question 4

Prolonged if over 35 sec (normally 25-35 seconds)

Answer 4

Partial Thromboplastin Time

Question 5

Coagulation Factor Assays (V, VII, VIII, IX, X, XI, XII)

Answer 5

● 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

Question 6

disorders of Primary Hemostasis are
those disorders that deal with ____

Answer 6

low platelet count or some
form of platelet dysfunction.

Question 7

PT and PTT should be normal in disorders of ____ hemostasis

Answer 7

primary

Question 8

Thrombocytopenia simply means low ____

Answer 8

Platelet count

Question 9

Thrombocytopenia can be due to either

Answer 9

○ Decreased Platelet production
○ Enhanced Platelet destruction

Question 10

Pathophysiology of thrombocytopenia - Examples of Decreased Production of Platelets-

Answer 10

■ Bone marrow failure (ex: Aplastic Anemia)
■ Malignant infiltration of the the bone marrow
■ Exposure to some meds, chemotherapy, or radiation
■ Significant nutritional deficiencies

Question 11

Pathophysiology of thrombocytopenia - Examples of Increased Destruction of Platelets

Answer 11

■ Immune Thrombocytopenia (ex: ITP)
■ Heparin-Induced Thrombocytopenia
■ Disseminated Intravascular Coagulopathy (DIC)
■ Hypersplenism (ex: Related to cirrhosis, lymphoma)
■ Septicemia

Question 12

Thrombocytopenia Exam and Lab Findings:

Answer 12

○ If significant Thrombocytopenia, Petechiae, Purpura, or
Ecchymosis may develop with little or no explanation.
○ Platelet count will be low on CBC.

Question 13

____ 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.

Answer 13

Petechiae

Question 14

____ 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.

Answer 14

Dry Purpura

Question 15

The finding of purpura on mucous
membranes (rather than the skin) is
sometimes referred to as ____

Answer 15

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.

Question 16

Thrombocytopenia: Treatment and Management

Answer 16

○ Treatment obviously depends on the
underlying condition causing the
Thrombocytopenia.

Question 17

An acquired autoimmune disorder characterized by isolated
thrombocytopenia, maybe without an apparent cause

Answer 17

ITP
● Immune Thrombocytopenic Purpura (previously called “idiopathic”)

Question 18

What is this

Answer 18

Wet purpura

Question 19

Epidemiology of ITP

Answer 19

● 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

Question 20

ITP Pathophysiology

Answer 20

○ 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.

Question 21

Primary vs secondary ITP

Answer 21

Primary ITP: Acquired immune thrombocytopenia without an apparent
cause
Secondary ITP: ITP associated with another condition with an inciting event

Question 22

ITP: Characteristic Signs and Symptoms

Answer 22

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.

Question 23

Diagnostic testing for ITP

Answer 23

○ 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

Question 24

ITP Treatment:

Answer 24

○ 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?)

Question 25

TTP

Answer 25

Thrombotic Thrombocytopenic Purpura (TTP)

Question 26

Thrombotic Thrombocytopenic Purpura (TTP)

Answer 26

● 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

Question 27

Pathophysiology of TTP

Answer 27

○ 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.

Question 28

Deficiency in the protease ADAMTS13 has been identified with ___

Answer 28

TTP

Question 29

Characteristic Signs and Symptoms of TTP

Answer 29

○ Most patients present with fever. ○ Thrombocytopenia ○ Microangiopathic hemolytic anemia ○ Renal impairment ○ Neurologic dysfunction is characteristic of the disease, but not always present.

Question 30

TTP Additional diagnostic testing:

Answer 30

○ Anemia on CBC ○ Elevated Lactate Dehydrogenase (LDH) ○ Reticulocytosis ○ Schistocytosis ○ Thrombocytopenia ○ Elevated BUN/Creatinine

Question 31

TTP Treatment and Management

Answer 31

○ 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

Question 32

Hemolytic Uremic Syndrome classic triad

Answer 32

○ Hemolytic Anemia ○ Thrombocytopenia ○ Renal Dysfunction (just like with TTP)

Question 33

What differentiates HUS from TTP?

Answer 33

Classically differentiated from TTP by absence of Neurologic symptoms. Although ¼ can get neurologic signs

Question 34

Hemolytic Uremic Syndrome pathophysiology

Answer 34

○ 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.

Question 35

Hemolytic Uremic Syndrome Characteristic Signs and Symptoms

Answer 35

○ 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

Question 36

Hemolytic Uremic Syndrome diagnostic testing

Answer 36

○ 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

Question 37

Hemolytic Uremic Syndrome Treatment and management

Answer 37

○ 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.

Question 38

von Willebrand’s Disease inheritence

Answer 38

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.

Question 39

von Willebrand’s Disease Pathophysiology

Answer 39

○ Normal vWF serves two main functions- ■ Molecule that adheres platelet to injured endothelium ■ Chaperone to Factor VIII, slowing its degradation

Question 40

Several types of vWD

Answer 40

■ 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

Question 41

von Willebrand’s Disease Characteristic Signs and Symptoms

Answer 41

○ 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.

Question 43

von Willebrand’s Disease Diagnostic Testing:

Answer 43

○ 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.

Question 44

von Willebrand’s Disease Treatment and Management

Answer 44

○ 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.

Question 45

disorders of Secondary Hemostasis are those that deal with ____

Answer 45

Factor deficiencies or dysfunctions within the Coagulation Cascade

Question 46

Disorders of Secondary Hemostasis include

Answer 46

○ Hemophilia A ○ Hemophilia B ○ Liver Disease-Induced ○ Vitamin K Deficiency

Question 47

Hemophilia A

Answer 47

Hemophilia A is hereditary bleeding disorder that is considered X-Linked Recessive.

Question 48

___ is the most common severe bleeding disorder

Answer 48

Hemophilia A

Question 49

Hemophilia A Pathophysiology

Answer 49

○ The disorder leads to a deficiency in Coagulation Factor VIII. ○ Factor IX is unable to activate Factor X, so coagulation is dysfunctional .

Question 50

Hemophilia A Characteristic Signs and Symptoms

Answer 50

○ Bleeds in deep tissue is characteristic. ○ Spontaneous Hemarthroses- Essentially diagnostic! ○ Can also bleed into muscles, GI tract, and base of tongue

Question 51

What is this called and indicative of?

Answer 51

Spontaneous Hemarthroses- Essentially diagnostic for hemophilia A

Question 52

Hemophilia A Diagnostic Testing

Answer 52

○ Because the Intrinsic Pathway is completely dependant on Factor VIII, PTT is prolonged with Hemophilia A. ○ Coagulation Factor VIII Assay will show decreased levels.

Question 53

Hemophilia A Treatment and Management

Answer 53

○ 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)

Question 54

Hemophilia B differences from A

Answer 54

● 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

Question 55

“Christmas Disease”

Answer 55

Hemophilia B

Question 56

Hemophilia B Treatment and Management

Answer 56

○ 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

Question 57

Vitamin K Deficiency pathophysiology

Answer 57

Vitamin K deficiency bleeding disorder can be caused by… ■ Warfarin therapy ■ Poor diet ■ Malabsorption ● Antibiotic-related diarrhea ● Inflammatory bowel disease ■ Biliary obstruction

Question 58

Vitamin K Deficiency Diagnostic Testing

Answer 58

○ 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

Question 59

Vitamin K Deficiency treatment

Answer 59

○ 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

Question 60

The liver is responsible for production of all coagulation factors except____

Answer 60

VIII and vWF.

Question 61

Characteristic Signs and Symptoms of Liver Disease-Induced coagulation issues

Answer 61

○ Any type of bleeding is a possible sign/symptom. ○ Assess for signs of liver failure (jaundice, caput medusae, ascites, etc)

Question 62

Diagnostic Testing for Liver Disease-Induced coagulation issues

Answer 62

○ Characteristically shows prolonged PT and PTT. ■ Administration of Vitamin K will not correct this ○ May see Thrombocytopenia secondary to hypersplenism.

Question 63

Liver Disease-Induced Treatment and Management:

Answer 63

○ 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.

Question 64

DIC

Answer 64

Disseminated Intravascular Coagulation

Question 65

Disseminated Intravascular Coagulation

Answer 65

● Uncontrolled activation of coagulation ■ → depletion of clotting factors and fibrinogen ■ Thrombocytopenia as platelets are used up

Question 66

DIC Pathophysiology

Answer 66

○ 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

Question 67

DIC Diagnostic testing

Answer 67

○ 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

Question 68

DIC Treatment and Management

Answer 68

○ 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

Question 69

HELLP Syndrome can progress to DIC

Answer 69

Hemolysis, Elevated Liver enzymes, Low Platelets

Question 70

DIC as a complication of pregnancy

Answer 70

● HELLP Syndrome can progress to DIC ● Hemolysis, Elevated Liver enzymes, Low Platelets ● Kidney injury ● High mortality rate ● Treatment includes delivery