Bleeding+Hemostasis Disorders

Primary Hemostasis Physiology

PP: platelet activation+adherence+aggregation→forms platelet plug at site of injury

E: vWF (causes platelets to be sticky)
fibrinogen (links platelets together→forms platelet plug)

Secondary Hemostasis Physiology

PP: serial+cascading activation of clotting factors at endothelial injury site/existing platelet plug→forms fibrin clot

E: extrinsic pathway→tissue injury
intrinsic pathway→factor XII activation

TX:
stop
protein C
protein S
plasminogen/plasmin system

Activated Partial Thromboplastin Time (aPTT)

measures+evaluates all clotting factors of intrinsic+common pathways of clotting cascade

measures in seconds it takes a clot to form

Prothrombin Time (PT)

measures+evaluates clotting factors of extrinsic+common pathways of coagulation cascade

Von Willebrand Disease (vWD)

PP: decreased activity of von willebrand factor (vWF) activity in blood

E: 1% US population
m/c congenital bleeding dx

type 1 (least severe)
m/c
75-80% pts
quantitative abnormality (too little) in vWF glycoprotein
no casual mutation in vWF gene

type 2
15-20% pts
qualitative abnormality in vWF glycoprotetin (vWF doesn’t work)
-2A
-2B
-2M
-2N

type 3 (most severe)
3% pts
quantitative abnormality (too little)
little-no vWF
mutation in vWF gene

CM: heavy menstrual bleeding (heavy day→soaking through tampon x 1-2 hours)
excessive bruising
epistaxis (10+ min+5x+/year)
prolonged bleeding

DX (type 1 vWD):
vWF activity→decreased
vWF factor antigen→decreased
vWF multimeter pattern→normal
aPTT (factor VIII clotting activity)→normal
platelet aggregation→decreased

TX (type 1 vWD):

NP: hematologist referral+follow-up
avoid contact sports

MX: mild/pre-surgery→DDAVP
menorrhagia→OCP

P: tx+prophx→normal life expectancy

Von Willebrand Factor (vWF) Function

glycoprotein binds platelets to endothelial surfaces→aggregates/clumps platelets together→platelet plug

contains binding site for factor VIII→prolongs factor VIII in circulation

Hemophilia A (Classic Hemophilia)

PP: inadequate thrombin formation→soft+friable clot→profuse bleeding→tamponade→rebleeding

E: congenital deficiency of factor VIII
x-linked recessive

CM: spontaneous bleeding
recurrent hemarthroses
1st episode→under 18 months (toddlers starting to cruise)
intracranial hemorrhage

DX: factor VIII assay→decreased
PTT→increased (mixing study corrects)

TX:
NP: avoid trauma

MX: synthetic factor VIII concentrate
IM injections

P: m/c death→intracranial hemorrhage
frequent mx tx→antibody development

Hemophilia B (Christmas Disease)

PP: inadequate thrombin formation→soft+friable clot→profuse bleeding→tamponade→rebleeding

E: congenital deficiency of factor IX
x-linked recessive

CM: spontaneous bleeding
recurrent hemarthroses
1st episode→under 18 months (toddlers starting to cruise)
intracranial hemorrhage

DX: factor IX assay→decreased
PTT→increased (mixing study corrects)

TX:
NP: avoid trauma

MX: synthetic factor IX concentrate
IM injections

P: m/c death→intracranial hemorrhage
frequent mx tx→antibody development

“Do the 5”

for hemophilia A+B

1. annual comprehensive checkup at hemophilia treatment center

2. hepatitis A+B vaccines

3. treat bleeds early+adequately

4. exercise+maintain healthy weight→protects joints

5. get tested regularly for blood-borne infections

Idiopathic/Immune Thrombocytopenic Purpura (ITP)

PP: pathogenic antibodies bind to platelets→accelerate clearance from circulation
body lacks compensatory platelet production

RF: children
recent viral illness/dx

E:
primary
isolated thrombocytopenia
idiopathic

secondary
isolated thrombocytopenia
2/2 autoimmune dx
-SLE
-lymphoma
-HIV
-hepatitis A/B

CM: petechiae
purpura
gum bleeding
menorrhagia
epistaxis
no fever+lymphadenopathy+hepatosplenomegaly (present→leukemia)

DX:
CBC→isolated thrombocytopneia
-acute→platelets under 20k
-chronic→platelets under 30-80k
hemoglobin→normal
hematocrit→normal
WBC count→normal

multiple+unexplained cytopenias→bone marrow aspiration+biopsy
r/o other dx

TX:
NP: hematologist referral
over 30k/chronic→monitor CBC serially
active bleeding→platelet transfusion
avoid trauma

MX: only with over 20k platelets/significant bleeding
1st line: PO prednisone
±IV IG

PO prednisone: platelets→improve x 3-7 days
IVIG: platelets→improve x 24-48 hours

over 30k post tx→2nd-line txs
-IV rituximab x4 months
-IV anti-d PRN
-IV IG
-SQ romiplostim x weekly
-PO eltronmbopag x daily
-PO avatrombopag x daily
-PO fostamatinab BID

P:
tx duration
platelets→improve x 3-7 days
IVIG→improve x 24-48 hrs

Thrombotic Thrombocytopenic Purpura (TTP)

PP: ADAMTS13 enzyme deficiency in vWF+shearing RBCs→vWF too long+too sticky→small vessel thrombosis/organ dysfxn/MAHA

E: adults
autoimmune dx
genetics
pregnancy
cyclosporine
clopidogren
bleomycin

CM:
classic pentad (25% pts)

• fever

• thrombocytopenia

• MAHA

• renal failure

• neuro deficits
  -h/a
  -somnolence
  -delirium
  -seizures
  -paresis
  -coma

DX:
CBC
normocytic anemia
thrombocytopenia

reticulocyte count→elevated

LDH→elevated
indirect bilirubin→elevated
haptoglobin→decreased
PT→normal
PTT→normal

peripheral smear→schistocytes

ADAMTS-13 inhibitor
autoimmune: presence→decreased activity
inherited: absence→deceased activity

TX:
NP: ER admission
hematology+critical care referral
pt edu→DX monitoring

MX:
1st line: plasma exchange x daily→platelet count+LDH normal for 2 days→taper
no platelet transfusions
kidney injury→hemodialysis
corticosteroids
monoclonal antibodies
monitor CBC
monitor hemolysis labs
monitor ADAMTS-13 activity

C: chronic renal failure

P: no plasma exchange→95% mortality
plasma exchange→85% survival rate

Hemolytic-Uremic Syndrome (HUS)

PP: toxin-mediated endothelial damage
triad
microangiopathic anemia
thrombocytopenia
acute kidney injury (AKI)

E: undercooked ground beef→e coli
children
under 5 y/o
m/c cause of peds AKI

CM:
prodrome
-abd pain
-vomiting
-bloody diarrhea

DX: hemolytic anemia
thrombocytopenia

CBC→normocytic anemia
reticulocytes→elevated

LDH→elevated
indirect bilirubin→elevated
haptoglobin→decreased
CrCl→elevated
PT→normal
PTT→normal
fibrinogen→normal

peripheral smear→schistocytes

thrombocytopenia

stool culture→e coli
stool assays→shiga toxin

TX:
IV fluids
monitor CBC+CMP
no abx
kidney injury→hemodialysis
frequent lab monitoring
ER admit+pediatric hematologist

Disseminated Intravascular Coagulopathy (DIC)

PP: too much+too little clotting at same time→uncontrolled IV coagulation→depletes fibrinogen+factors→consumes platelets→low platelet count
microthrombi→consumption→hemorrhage

E: acute+serious mx incident
-sepsis
-hypoxia
-massive tissue injury
-labor
-delivery
-burns
-snake bites

CM: sudden onset hemorrhage→80-90%
epistaxis
hematuria
melena
BRBPR
thrombi
venipuncture sites→bleeding/oozing
purpura fulminans

DX: fibrinogen→decreased
PT→increased
PTT→increased
fibrin split productions→elevated
d dimer→elevated
platelets→decreased

peripheral smear→schistocytes

TX: hospitalization+hematologist referral
tx underlying cause
establish lab baselines+follow
transfusions
anticoagulation

P: mortality rate→50-60%

Hemolysis Elevated Liver Enzymes Low Platelets Syndrome (HELLP)

PP: microangiopathic blood smear+HELLP findings
within preeclampsia/eclampsia spectrum

RF: women+preeclampsia
advanced maternal age
multiparity

E: unknown
preeclampsia?
severe form of DIC?

CM: abdominal/epigastric apin
nausea
vomiting
malaise

DX:
80% pts
increased BP
proteinuria

peripheral smear
burr cells
schistocytes
echinocytes

indirect bilirubin→elevated
LDH→over 600
haptoglobin→low
LFT→elevated (2x ULN)
thrombocytopenia (under 100k platelets)

TX: 1st line→deliver baby (vaginal)
stabilize pt+fetus
blood transfusion PRN
coagulation factor transfusion PRN
monitor UOP+renal function
tx HTN

C: DIC
placental abruption
acute renal failure
pulmonary edema
liver hematoma