Bleeding disorders- part 1 Flashcards
What does a mucocutaneous bleed indicate? Is this considered primary or secondary?
likely qualitative/quantitative platelet defects
primary hemostasis
What does a joint/soft tissue bleed indicate? Is this considered primary or secondary?
Likely disorders of coagulation factors
What lab test should you order for a bleeding pt?
CBC
Blood smear
Coag panel
CMP
What modern test is used to calculate the bleeding time?
Platelet function analyzer (PFA-100)
What does a prolonged PTT indicate?
deficiencies of Factors VIII or IX –hemophilia
What test would you order if you want to monitor heparin?
Heparin = monitor with aPTT = Intrinsic pathway
PTT detects deficiencies of the ____ pathway
intrinsic
What does PTT stand for?
Partial thromboplastin time (PTT, aPTT)
What does PT stand for ? It measures the ____ pathway
Prothrombin Time
Extrinsic pathway
When evaluating the PT, Add ______ - reacts with ____ to initiate clotting through extrinsic/common pathway
thromboplastin (TF)
VIIa
Would order ____ when monitoring Warfarin. It is ____ dependent
PT
Vit K dependent, think extrinsic pathway
Which clotting factor has the shortest half life?
Factor VII
** What does an increased INR indicate?
higher risk of a bleed
** What does an decreased INR indicate?
higher risk of developing a clot
Defect in the extrinsic pathway causes an (increase/decrease) of ____
increase in PT
Defect in the intrinsic pathway causes an (increase/decrease) of ____
increase in aPTT
What will a defect in the common pathway cause?
increase in both PT and aPTT
**How do disorders of primary hemostasis present? What do they affect?
mucous membrane bleeding, epistaxis, and petechiae.
bleeding time and platelet count.
**How do disorders of secondary hemostasis present? What do they affect?
hemarthrosis, intracerebral hemorrhage, and deep tissue hematomas.
affect PT and PTT
**What things will a mixed bleeding disorder affect?
bleeding time and platelet count, as well as PT and PTT
When would you need to order both a PT and aPTT?
transitions between heparin and warfarin therapy
assessing pts with s/s of hemorrhage or thrombosis (or about to have a medical procedure)
Hemophilia A: congenital deficiency of coagulation _____
Hemophilia B: congenital deficiency of coagulation ____
factor VIII
factor IX
What is a hallmark s/s of hemophilia?
bleeding into a joint, usually the knee
** What is the frequency of hemophilia A? How is it inherited?
1 per 5000 live male births
Most common X-linked genetic disease
** What is the frequency of hemophilia B? How is it inherited?
1 in 25,000 live male births
X-linked recessive, leading to affected males and carrier females.
What percentage of hem A patient develop antibodies to the clotting factors? Hem B?
Approximately 30% of patients with hemophilia A
< 5% of patients with hemophilia B
What lab findings would be expected in a hemophilia pt?
Low factor VIII/IX
aPTT is prolonged
PT/INR and CBC is normal
Normal hemostasis requires at least ____ of factor VIII activity
25%
** mild hem A presents with a minor bleed, what is the treatment? Major bleed?
minor: DDAVP
major: DDAVP or factor VIII concentrate
** mod/severe hem A presents with a minor bleed, what is the treatment? Major bleed?
Minor: Factor VIII concentrate
Major: Factor VIII concentrate
** mild/mod/severe hem B presents with a minor bleed, what is the treatment? Major bleed?
minor: Factor IX concentrate
major: factor IX concentrate
What is the normal treatment regimen for a severe hem pt?
require infusions of factor concentrate up to 3 times a week to prevent recurrent joint bleeding
Hem pt with arthritis symptoms, prescribe _____. Why?
celecoxib (Celebrex), works on COX2
NSAIDs and aspirin should be avoided due to the increased risk of bleeding from inhibition of platelet function
What is the most important life-threatening complication for a hem pt?
Intracranial hemorrhage and hemorrhages into the soft tissue
What is the MC cause of death in hem pts?
due to transfusion-obtained HIV/AIDS and hepatitis/cirrhosis
_____ is the most common inherited bleeding disorder
Von Willebrand Disease
vWF is a large multimeric glycoprotein that binds to its receptor,______, bridging platelets together and tethering them to the site of vascular injury.
platelet glycoprotein Ib
**Type 1 vWD is a ____ defect. How is it inherited? What is the clinical manifestation?
quantitative (not enough vWF)
autosomal dominant
zero to severe bleeding
**Type 2 vWD is a ____ defect. How is it inherited? What is the clinical manifestation?
Qualitative defect (dysfunctional vWF)
Commonly autosomal dominant (sometimes autosomal recessive)
moderate to severe bleeding
**Type 3 vWD is a ____ defect. How is it inherited? What is the clinical manifestation?
quantitive defect (almost zero or zero vWF)
autosomal recessive
severe bleeding
What kind of vWD is most common?
Type 1 is most common, almost 3/4 of the cases
What are the MC s/s of vWD?
nosebleeds
hematomas
prolonged bleeding from trival wounds
oral cavity bleeding
excessive menstrual bleeding in woman
What are the lab findings for a pt with vWD?
prolonged bleeding time (type 1 vWD can be have a normal bleeding time)
aPTT is mildly prolonged in some pts due to low levels of factor VIII (can be normal)
PT should be NORMAL
Levels of vWF vary with ____ and ____
stress
blood type
What blood type has the lowest levels of vWF?
Patient with type O blood have the lowest levels of vWF (approximately 50-75% of normal)
What are the treatment options ofr vWD?
desmopressin (DDAVP): mild bleeding only
recombinant von Willebrand factor (rVWF)
von Willebrand factor/factor VIII (vWF/FVIII) concentrates
**_____ is most prevalent among individuals of Ashkenazi Jewish descent. How is it inherited? What is the treatment?
Factor XI Deficiency
autosomal recessive
Factor XI concentrate, if not available use FFP
Thrombocytopenia is dangerous because ??
inability to form a primary plug or secondary clot
Thrombocytopenia usually results from _____ or _____
increased destruction or decreased production
If plts are below 10K, you are at a high risk of ____
spontaneous hemorrhage
If plts are below 50K, you are at a high risk of ____
increased bleeding during invasive procedures and in trauma (non-CNS)
If plts are below 100K, you are at a high risk of ____
increased bleeding/complications during invasive procedures in closed spaces (CNS, eye)
What type of thrombocytopenia is HIT considered?
Destructive/Consumption Thrombocytopenia
Name 2 causes of Splenomegaly/Hypersplenism. What is the treatment?
mechanical causes (e.g. liver disease) or malignant causes (e.g. lymphoma)
Treatment needs to address underlying causes or remove the spleen
IMMUNE THROMBOCYTOPENIC PURPURA, what is happening?
patients form auto-antibodies against antigens on the PLT surface
This results in their destruction
**Name the most common ITP pt population. Name some additional types of pts
Commonly seen in children following an upper respiratory or viral infection (60%)
Rare in adults: lymphoma, lupus, Hep C, HIV and H. pylori
How does ITP present
sudden appearance of a petechial rash, bruising, and/or bleeding in an otherwise healthy child
40% of pt have mucosal bleeding
Intracranial hemorrhage is the most severe but rare
How do you dx immune thrombocytopenia purpura?
Isolated thrombocytopenia (platelet count <100,000/microL), with otherwise NORMAL blood counts and peripheral blood smear
abdominal ultrasound
PT and PTT will be NORMAL
if pt does have an abnormal WBC or blood smear it is NOT ITP, need to go find the cause of the abnormal WBC/blood smear
Why would you order an abdominal ultrasound on a pt if you suspect ITP?
to rule out splenomegaly
If ITP is mild/moderate, what do you do?
watchful waiting
Name 3 conditions in which would require pharmacologic intervention for a pt with ITP
Severe thrombocytopenia (platelets <10,000/microL) with signs of substantial cutaneous bleeding
Moderate thrombocytopenia (platelets <20,000/microL) with mucosal bleeding
Past or anticipated factors that increase bleeding risk (such as recent head trauma)
Why or why not would you want to give a pt with ITP anitplatelets or DOACs?
should be avoided until ITP has resolved
If ITP does not get better on its own, what is the recommended treatment?
Corticosteroids are FIRST line therapy
Oral prednisone, IV methylprednisolone, IV or oral dexamethasone
IV immunoglobulin (IVIG) may be added initially
Platelet transfusions may be given for serious bleeding, not mild
Splenectomy may be necessary, if thrombocytopenia persists for more than 6 months
drug related platelet destruction mechanism is _____ in most cases
immune-mediated
Drug-related destruction typically presents as severe thrombocytopenia and mucocutaneous bleeding _____ after exposure to a new drug
7-14 days
____ are a well known cause of drug related thrombocytopenia
antibiotics
sometimes with drug related destruction thrombocytopenia ____ are needed to reduce antibody titers
corticosteroids
Bleeding-associated consumption thrombocytopenia usually happens when ????
What is the treatment?
Massively bleeding patients can consume PLTs at rates beyond which they can be produced by the bone marrow
blood product infusion and surgical intervention to stop the bleed
Hypoproliferative Thrombocytopenia most commonly arises from ???
bone marrow failure
Name a few common hypoproliferative disorders
Leukemia / lymphoma / myelodysplasia / aplasia
Cancers metastatic to bone marrow
Severe viral infections (e.g. CMV, HIV)
Radiation or chemotherapy treatment
Refers to a group of disorders wherein PLT counts are typically normal. Is congenital or iatrogenic/acquire more common?
Qualitative PLT Disorders
iatrogenic or acquired is more common
Similar to thrombocytopenia, _____ manifest as mucous membrane bleeding. What is the treatment?
qualitative PLT disorders
transfusion of normal donor plts
What is the MC cause of acquired plt dysfunction?
aspirin, clopidogrel (Plavix), and NSAIDs (e.g. ibuprofen)
Aspirin and clopidogrel are (irreversible/ reversible) inhibitors of PLT function
irreversible
NSAIDs are (irreversible/ reversible) inhibitors of PLT function
reversible, normal plt function returns 12-24 hours after clearance
For patients on aspirin or clopidogrel scheduled for invasive procedures, the drugs should be stopped ____ days before the planned intervention. How long for NSAIDs?
5-10
24-48 hours
thrombotic microangiopathies (TMAs) include:
______ and _____
Thrombotic thrombocytopenic purpura (TTP)
Hemolytic-uremic syndrome (HUS).
____ and ____ are characterized by thrombocytopenia, due to the incorporation of platelets into thrombi in the microvasculature, and microangiopathic hemolytic anemia, which results from shearing of erythrocytes in the microcirculation
Thrombotic thrombocytopenic purpura (TTP)
and
Hemolytic-uremic syndrome (HUS).
Patients with ____ have unusually large multimers of von Willebrand factor (vWF) in their plasma and lack a plasma protease that is responsible for the breakdown of these ultralarge vWF multimers (ADAMTS13) or have antibodies against the ADAMTS13 molecule.
What am I?
Thrombotic Thrombocytopenic Purpura
Thrombotic Thrombocytopenic Purpura is most common in what pt population?
more common in females
more common in black pts
**ADAMTS13 molecule, thinking ???
Thrombotic Thrombocytopenic Purpura
What is the role of ADAMTS13? What is the result?
breaks down vWF when it is no longer needed
small blood clots form more frequently
What is the clinical presentation of TTP?
neurologic dysfunction: mental status, seizures, hemiplegia, paresthesias, visual disturbance, and aphasia.
anemia
thrombocytopenia
petechiae
Fever in 50% of pts
dark urine from hemoglobinuria
CBC usually reveals a normal or slightly elevated total white blood cell count.
Hemoglobin is moderately depressed at 8-9 g/dL.
Platelet count generally ranges from 20,000-50,000
Peripheral smear reveals moderate-to-severe schistocytosis
PT and aPTT are normal
Fibrinogen is normal/high to high range
Direct Coombs test should be negative
What am I?
Thrombotic Thrombocytopenic Purpura
What is the treatment for Thrombotic Thrombocytopenic Purpura?
full plasma exchange with FFP
Second line treatment includes: rituximab, corticosteroids, IVIG, vincristine, cyclophosphamide, and splenectomy.
What am I?
Thrombotic Thrombocytopenic Purpura
_____ is a clinical syndrome characterized by progressive renal failure that is associated with microangiopathic hemolytic
hemolytic-uremic syndrome (HUS)
**What is the MCC of acute renal failure in children?
Hemolytic-Uremic Syndrome (HUS)
Damage to endothelial cells is the primary event
The cardinal lesion is composed of arteriolar and capillary microthrombi and red blood cell (RBC) fragmentation
What am I?
Hemolytic-Uremic Syndrome (HUS)
What is prodromal gastroenteritis?
Prodrome of fever, bloody diarrhea for 2-7 days before the onset of renal failure
Prodromal gastroenteritis
Irritability, lethargy
Seizures
Acute renal failure
Anuria
HTN
Edema/volume overload
Pallor
What am I?
Hemolytic-Uremic Syndrome (HUS)
**_____ associated HUS is the classic, primary or epidemic form of hemolytic-uremic syndrome (HUS).
Shiga-like toxin
**In North America and Western Europe, 70% of cases Stx–associated HUS are secondary to _______
Escherichia coli serotype O157:H7
If suspecting HUS, what tests should you order?
Obtain a stool sample for E. coli and Shigella
BMP will demonstrate elevated BUN/CR
CBC will reveal severe anemia and varying degrees of thrombocytopenia
Peripheral smear will show schistocytes
Bilirubin and LDH may be mildly elevated
Disseminated Intravascular Coagulopathy, what does aPTT, PT and fibrinogen levels look like?
prolonged aPTT and PT
low plts
decreased fibrinogen levels
_____ results from uncontrolled local or systemic activation of coagulation, which leads to thrombocytopenia and depletion of coagulation factors and fibrinogen
Disseminated intravascular coagulation (DIC)
What is the layman’s terms way of explaining DIC.
blood clotting out of control which uses up all the platelet and clotting factors then the pt bleeds with the slightest injury
What are some causes of DIC (Disseminated Intravascular Coagulopathy)
S = Sepsis
T = Trauma
O = Obstetric complications (ex: Preeclampsia)
P = Pancreatitis (Acute)
M = Malignancy (esp. Blood and brain cancers)
N = Nephrotic syndrome
T = Transfusion (hemolytic rxn)
STOP Making New Thrombi
Bleeding at multiple sites intravenous catheters or incisions, and may be widespread (purpura fulminans) with purpura and petechiae.
What am I?
DIC
Progressive thrombocytopenia (rarely severe)
Prolongation of the activated partial thromboplastin time (aPTT) and prothrombin time (PT)
Low levels of fibrinogen
D-dimer levels as well as other FDPs are elevated due to the activation of coagulation and diffuse cross-linking of fibrin.
Schistocytes on the blood smear, due to shearing of red cells through the microvasculature, are present in 10-20% of patients.
What am I?
DIC
What are the 6 steps in the treatment of DIC?
I. Assess for underlying cause of DIC and treat.
II. Establish baseline platelet count, PT, aPTT, d-dimer, fibrinogen.
III. Transfuse blood products only if ongoing bleeding or high risk of bleeding:
IV. Follow platelets, aPTT/PT, fibrinogen every 4–6 hours or as clinically indicated.
V. If persistent bleeding, consider use of heparin (initial infusion, 5–10 units/kg/h); do not administer bolus.
VI. Follow laboratory parameters every 4–6 hours until DIC resolved and underlying condition successfully treated
