HIgh INR
Etiology
- Some anticoagulants;
- Decreased synthesis of clotting factors (liver disease, Vitamin K deficiency including malnutrition, malabsorption, antibiotics);
- Increased consumption of clotting factors (sepsis/DIC)
PT
What does it test for?
Extrinsic and common pathway
PTT
What does it test for?
Intrinsic and common pathway
High PTT
Etiology?
- Some anticoagulants;
- Von Willebrand disease
- Hemophilia
- Antiphospholipid antibodies
- Sepsis/DIC
HIgh fibrinogen
Etiology
Acute phase reactant
Pregnancy
Low fibrinogen
Etiology
DIC
Liver failure
Acute phase reactant
What does it include?
C3, C4, fibrinogen, ESR, CRP, ferritin, hepcidin
D-dimer–high
Etiology
PE/DVT Arterial clots Sepsis/DIC Malignancy Recent surgery or trauma Liver disease Pregnancy
Coagulation profile
Plt, PT, PTT, D-dimer, fibrinogen
Algorithm for investigation of abnormal coagulation tests.
If PT or PTT and PT both prolonged, what’s your next step?
Give Vitamin K
Algorithm for investigation of abnormal coagulation tests.
PT or PTT and PT both prolonged s/p Vitamin K
- If responded–>Vitamin K deficiency
2. If not responded–>Liver disease assessment
Algorithm for investigation of abnormal coagulation tests.
PT or PTT and PT both prolonged 2/2 not vitamin K nor liver disease
Check mixing study
Algorithm for investigation of abnormal coagulation tests.
If Mixing study corrected
Due to factor deficiency
- Von Willebrand disease;
- Specific factor activity levels
Algorithm for investigation of abnormal coagulation tests.
If Mixing study not corrected
Due to antibody presentation
- Check antiphospholipid antibodies;
- Specific factor inhibitors.
Normal hemostasis
Intrinsic pathway factors
XII, XI, IX, VIII
Normal hemostasis
Intrinsic pathway factors
What is the test for?
PTT
Normal hemostasis
Extrinsic pathway factors
VII
Normal hemostasis
Extrinsic pathway factors
What is the test for?
PT
Normal hemostasis
What is the common pathway factors
X, V, II, fibrinogen
Prolonged PT, normal aPTT
DDx
Factor VII deficiency DIC Liver disease Vitamin K deficiency Warfarin ingestion
Normal PT, prolonged aPTT
DDx
Deficiency of VIII, IX, XI or XII;
von Willebrand disease (if severe and factor VIII level is low);
Heparin exposure
Prolonged PT and aPTT
DDx
Deficiency of factor V, X, II or fibrinogen; Severe liver disease; DIC; Vitamin K deficiency; Warafin use; Heparin overdose;
Normal PT and aPTT
DDx
Platelet dysfunction (acquired and congenital);
von Willebrand disease (if mild and factor VIII level is not too low);
Scurvy;
Ehlers-Danlos syndrome;
Hereditary hemorrhagic telangiectasia;
Deficiency of factor XIII
Bleeding into muscles and joints
Humoral clotting factor disorders
Mucosal bleeding
Primary hemostasis
Bleeding disorders
What signs in women menstrual history indicating underlying bleeding disorder?
Nighttime “flooding”;
Passing clots larger than a quarter;
Duration longer than 8 days;
Development of iron deficiency.
Congenital bleeding disorder
Hemophilia A and B
What is the genetic?
X-linked recessive
Congenital bleeding disorder
Hemophilia A and B
What are the deficient factors?
Hemophilia A: VIII
Hemophilia B: XI
Congenital bleeding disorder
Hemophilia A and B
Sx of severe hemophilia?
Factor level <1%
Joint bleeding, retroperitoneal bleeding, intramuscular bleeding and intracranial bleeding;
Children: bleeding after circumcision or loos of deciduous teeth.
Congenital bleeding disorder
Hemophilia A and B
Sx of moderate hemophilia?
Factor level between 1% to 5%
Present in adult, unlikely to be spontaneous
Congenital bleeding disorder
Hemophilia A and B
Sx of mild hemophilia?
Factor level>5%
Present in adult, unlikely to be spontaneous
Congenital bleeding disorder
Hemophilia A and B
What are the concerns for older patients?
HIV and HCV infection from blood product transfusion
Congenital bleeding disorder
Hemophilia A and B
Rx
Replacing factor VIII and IX
Congenital bleeding disorder
Hemophilia A and B
What are the complications 2/2 to treatment?
Antibody development to factor VIII and IX.
Congenital bleeding disorder
Hemophilia A and B
How to test alloantibodies against VIII and IX?
Bethesda titer
Congenital bleeding disorder
Hemophilia A and B
What is the typical lab results show?
Prolonged aPTT and normal PT;
aPTT mixing study will fully correct;
Measure baseline factor activity/
Congenital bleeding disorder
von Willebrand disease
Epi:
Most common inherited bleeding disorder.
Congenital bleeding disorder
von Willebrand disease
Sx:
Nosebleeds in children, easy bruising, bleeding gums, postsurgical bleeding, GYN problems
Congenital bleeding disorder
von Willebrand disease
What are the GYN presentations?
Heavey menstrual bleeding;
Endometriosis;
Miscarriages
Postpartum hemorrhage
Congenital bleeding disorder
von Willebrand disease
How many types of VW disease are there?
3
Congenital bleeding disorder
von Willebrand disease
Dx:
vWF antigen and activity level <30%; Factor VIII levels may be normal or low; Platelet function analyzer-100 (PFA-100) is prolonged; PT normal; PTT may be normal or slightly prolonged.
Congenital bleeding disorder
von Willebrand disease
Treatment for heavy menstrual bleeding?
Estrogen-containing oral contraceptives;
Desmopressin;
Antifibrinolytic agents such as tranexamic acid or e-aminocaproic acid during menses
Congenital bleeding disorder
von Willebrand disease
Rx:
Desmopressin preoperative at surgical prophylaxis
If severe bleeding episodes or prophylaxis for major surgeries- give factor VIII and vWF
Congenital bleeding disorder
von Willebrand disease
Type 2
Production of an abnormally functioning vWF molecules
Congenital bleeding disorder
von Willebrand disease
Type 3
Near lack of vWF, very low factor VII levels
Acquired bleeding disorder
Coagulopathy of liver disease
Which factor is not produced in liver?
Factor VIII, produced in extrahepatic endothelia cell.
Acquired bleeding disorder
Coagulopathy of liver disease
What is the lab results?
Prolonged PTT and PT;
Low fibrinogen level;
Supranormal factor VIIIlevels
Acquired bleeding disorder
Coagulopathy of liver disease
Rx
If bleeding:
Cryoprecipitate, FFP and platelet
If vitamin K deficiency–> Vitamin K
Acquired bleeding disorder
Acquired hemophilia
Presentation
Elderly people without family or PMHx of bleeding disorder;
Acute new onset bleeding;
Mucocutaneous or intramuscular
Acquired bleeding disorder
Acquired hemophilia
Lab findings
Normal PT;
Significantly prolonged aPTT;
1:1 mixing study unsuccessful at completely correting the aPTT
Acquired bleeding disorder
Acquired hemophilia
Mechanism
Autoantibody against factor VIII
Acquired bleeding disorder
Acquired hemophilia
Etiology
Associated with underlying disease: SLE Lymphoproliferative disorder Solid tumors More common idiopathic
Acquired bleeding disorder
Acquired hemophilia
Rx
Immunosuppression to eradicate inhibitor;
Recombinant activated factor VII
Acquired bleeding disorder
DIC
Lab features:
Elevated PT (due to consumption of factor VII);
Elevated PTT;
Low fibrinogen;
Elevated D-dimers
Low plt;
Microangiopathic hemolytic anemia with schistocytes on the peripheral blood smear
Acquired bleeding disorder
DIC
Rx
- Underlying causes;
- If bleeding or at risk for bleeding–> plt, ffp, or replacing clotting factors or cyroprecipitate to replace fibrionoten
ITP
What to test if found to have ITP
HIV, hepatitis (HBV, HCV), MPNs, Collagen vascular disease
ITP
What to do if plt<10
Spontaneous bleeding, bleeding precautions
ITP
What to do if plt>30
NTD
ITP
what to do if plt<30
Dexamethasone->IVIG->Rituximab->Romiplostin/Splenectomy
ITP
What to do if plt<50 and needs surgery
IVIG and transfuse
ITP
What to do if plt<50 and bleeding
IVIG and plt transfuse
ITP
What to do if plt<100 with intracranial bleeding
IVIG and plt transfusion
ITP
Plt threshold for central line
> 20
ITP
plt threshold for abdominal tap
> 30
ITP
Plt threshold for spinal tap
> 50