Bleeding Disorders

Question 1

Hemophilias

Answer 1

hemophilia A - factor 8 (VIII) deficiency
-MC*

hemophilia B - factor 9 (IX) deficiency
-Christmas disease

congenital clotting disorders

• X-linked recessive (so–>affects males)
• Severe pain in weight-bearing joint (hemophilic arthropathy)*

Labs: Instrinsic pathway affected so aPTT is long. Bleeding time is normal in hemophilia

Question 2

Platelet disorders

Answer 2

1. Dysfunction (acquired or congenital)
2. Splenic spequestration
3. Increased destruction
4. Impaired production

Question 3

Signs of bleeding

Answer 3

Petechiae (<2mm)

Purpura (2-10mm)

Ecchymosis (>1cm)

Question 4

What are the 4 components of a basic screen for a patient you suspect has a bleeding disorder?

Answer 4

1. CBC
2. Peripheral smear
3. PT/INR, aPTT
4. Bleeding time

Question 5

Platelet counts

Answer 5

Normal:
150,000 -450,000/mm3

Thrombocytopenia:
<100,000/mm3

Question 6

When does spontaneous bleeding occur?

Answer 6

<20,000/mm3 platelets

Question 7

Bleeding time

Answer 7

the measure of time from bleeding to hemostasis (coagulation)

Prolonged bleeding time:

1. Platelet disorder (ex. von Willebrand’s Disease)
2. Severe thrombocytopenia

Question 8

What are the 3 stages of hemostasis

Answer 8

Just after vessel injury…

1. Vasoconstriction
   “vascular spasm”
   -more effective in small vessels
2. PRIMARY Hemostasis/Platelet plug formation:
   - activated by von Willebrand factor
   - platelets adhere to exposed collagen, release ADP and thrombaxane A2
3. SECONDARY Hemostasis/Coagulation cascade:
   - formation of fibrin from fibrinogen
   - Extrinsic, Instrinsic, and Common pathways

Question 9

What do Protein C, S, and ATIII do?

Answer 9

regulate clot formation.

If you don’t have these, you clot TOO MUCH!

Question 10

Prothrombin Time (PT)

Answer 10

• Extrinsic pathway (or common)

- For monitoring Warfarin

Question 11

PTT or aPTT (Activated partial thromboplastin Time)

Answer 11

• Intrinsic pathway (or common)
• For monitoring heparin therapy (not LMWH)

-Significant for Hemophilia, vW disease, Vitamin K deficiency

Question 12

INR (International Normalized Ratio)

Answer 12

-more accurate, standardized way of looking at PT (extrinsic pathway)

Question 13

MC sites of bleeding for hemophilias A & B

Answer 13

• Joints (spontaneous hemarthrosis, is sign of severe disease)
• Muscles
• Skin
• GI
• GU

Question 14

Hemophilia A: Labs

Answer 14

• Platelets and PT are normal

- aPTT will be prolonged**

Question 15

Hemophilia A: treatment

Answer 15

• Factor VIII infusions
• Desmopressin
• AVOID aspirin

Question 16

Dysfunctional platelets

Answer 16

Acquired versus congential

• Acquired (MC)**
  ex. Drugs, uremia, alcoholism, myeloproliferative disease

LABS: prolonged bleeding time (otherwise normal)

TX:

• stop offending drug
• hemodialysis in uremic pt
• platelet transfusion if serious bleeding

Question 17

Platelets and the spleen

Answer 17

Splenomegaly/hypersplenism = thrombocytopenia

Post-splenectomy = (reactive) thrombocytosis

Question 18

Platelet disorders: Increased destruction

Answer 18

ITP (idiopathic thrombocytopenic purpura)

-autoimmune destruction

Question 19

Platelet disorders: Platelet consumption

Answer 19

1. TTP (thrombotic thrombocytopenic purpura)
2. HUS (hemolytic-uremic syndrome)
3. DIC (disseminated intravascular coagulation)

Question 20

ITP (idiopathic thrombocytopenic purpura)

Answer 20

-antibody mediated destruction of platelets

Primary ITP: not related to another condition
Secondary ITP: related to another condition (ex. CLL, SLE, HIV)

Question 21

Acute ITP

Answer 21

• kids 2-4
• IgG associated
• preceeded by viral URI
• Self-limited

Question 22

Chronic ITP

Answer 22

Females> males
20-50 yrs
-insidious onset
-usually secondary ITP, associated with another condition

Question 23

ITP:signs

Answer 23

• petechiae, purpura
• epistaxis, oral bleeding
• NO splenogmegaly

Question 24

ITP: labs

Answer 24

Platelets often below 20,000

Coagulation studies normal
BM–> increased megakaryocytes

Question 25

ITP: treatment

Answer 25

Acute: usually children don't need treatment Chronic ITP: HIGH dose dexamethasone or prednisone***

Question 26

HIT (heparin-induced throbocytopenia)

Answer 26

- IgG autoantibody against complexes of heparin and platelet factor 4 - Associated with arterial and venous thrombosis**** Tx: stop heparin

Question 27

TTP (thrombotic thrombocytopenic purpura)

Answer 27

Microangiopathic hemolytic anemia with thrombocytopenia*** -RBCs are getting sliced on the fibrin and platelets in vessels Symptoms: - abdominal pain (pancreatitis is common) - Jaundice - fever, fatigue, toxic-appearing - Neuro findings

Question 28

IF a child presents with what looks like TTP folllowing E. coli infection what could it be?

Answer 28

HUS (hemolytic uremic syndrome) Sx: bloody diarrhea before onset -microangiopathic hemolytic anemia + thrombocytopenia** - NO neuro findings - Renal failure predominates**

Question 29

TTP and HUS: Labs

Answer 29

- Microangiopathic hemolytic anemia 1. Increased retics 2. Increased LDH 3. Increased indirect bilirubin 4. Negative Coombs test Schistocytes (helmet cells) on peripheral smear -Normal coagulation tests

Question 30

TTP-HUS: treatment

Answer 30

Corticosteroids*** - plasmapheresis - Rituximab if refractory

Question 31

DIC (Disseminated Intravascular Coagulation)

Answer 31

First, extensive thrombosis Second, bleeding/hemorrhage once all the platelets are used up

Question 32

DIC: labs

Answer 32

Decreased platelets Decreased fibrinogen Increased PT and PTT Increased D-Dimer -Schistocytes on peripheral smear

Question 33

DIC: treatment

Answer 33

Transfusion support** - Cryoprecipitate - FFP - Platelet transfusion - RBC transfusion

Question 34

Von Willebrand's Disease

Answer 34

- Autosomal dominant - MC coagulopathy - Reduced levels of factor VIII antigen or ristocetin cofactor Type 1 is most common (decreased vWF) Acquired vW disease --> bone marrow malignancy MC*

Question 35

What does Von Willebrand Factor do?

Answer 35

1. makes platelets adherent to subendothelium | 2. Plasma carrier of factor VIII

Question 36

Von Willebrand disease: Labs

Answer 36

Prolonged bleeding time (hemophilia has normal bleeding time) - Low vWF - INR normal

Question 37

Von Willebrand disease: treatment

Answer 37

1. Desomopressin for type | - releases stored vWF from endothelial cells