Bleeding disorders Flashcards
What are visible signs of bleeding
Petechiae: <2mm, subQ bleeding, do NOT blanch (occur periorbital 2/2 vomiting)
Purpura: 2-10 mm, palpable or not
Ecchymosis: >1cm, extensive areas of bruising
What labs do you get when you suspect bleeding
CBC w/ PLT count
peripheral smear
PT/INR, aPTT
Bleeding time
What is a platelet count
# of PLT (thrombocytes) only, not quality Normal: 150-450 <40= prolonged bleeding from vascular injury can occur <20= spontaneous bleeding can occur
What is bleeding time
Measure of time for hemostasis (clot formation)
Screen microvascular and platelet function
Prolonged in platelet disorders and severe thrombocytopenia
How does hemostasis occur after an injury (overview of steps)
- Vasoconstriction
- Platelet plug formation
- Coagulation cascade
What happens during vasoconstriction
Vascular spasm; occurs immediately after injury
Smooth muscle on damaged vessels constricts and reduces amount of blood flow to the area, limiting blood loss
Collagen is exposed and promoted platelets to adhere
What happens during platelet plug formation
Platelets clump together (adhesion) on damaged endothelium and form a plug, then degranulate (thromboregulation)
Plug formation is activated by vWF
Platelets adhere to exposed collagen and release ADP and thromboxin A2= increased vasoconstriction
What happens during the coagulation cascade
Secondary hemostasis: clotting factors are activated after platelet plug forms
Causes formation of fibrin
Comprised of: Intrinsic pathway, Extrinsic pathway, and Common pathway
What helps regulate clotting in the coagulation cascade to ensure too much clotting doesn’t happen
Protein C, S, and ATIII
A deficiency in these makes you more likely to clot!
What happens in the intrinsic pathway
After damaged surface, factor XIIa, XIa, IXa, VIIIa go to Xa
Xa activates thrombin, fibrin, XIIIa, and clot is formed
What happens in the extrinsic pathway
After trauma, factor VII* and VIIa form tissue factor
Those along with factor X go to Xa
Xa activates thrombin, fibrin, XIIIa, and clot is formed
What is PT
Prothrombin time; Prolonged with abnormalities in the extrinsic* (or common) pathway Used to monitor warfarin therapy Assess liver function and damage DIC
What is PTT or aPTT
Activates partial thromboplastin time
Prolonged with abnormalities in the intrinsic* (or common) pathway
Used to monitor UFH therapy (NOT LMWH)
Hemophilia, vW disease, liver damage, VK deficiency
DIC
What is INR
More accurate reflection of PT since PT is not standardized
Standardized ratio of PT:control
Results independent of reagents or methods used
Goal level is dependent on underlying need for anticoagulation (this is why we use it to monitor warfarin)
What are clotting disorders (cant clot well)
Associated with excessive or repetitive bleeding at unusual sites with normal activity
Can be congenital or acquired
What are Hemophilia A&B
A: factor VIII deficiency (MC)
B: IX deficiency (christmas dz)
-both are congenital bleeding disorders
Both hemophilia A&B are
X linked, recessive d/o that affect males mainly, or females born to affected dad and carrier mom
Severity correlates to factor levels (<1% factor level= extremely severe)
How do Hemophilia A&B present
Most ASx in first few months of life
First episode of Sx bleeding w/in first 2 years of life
Sever pain in weight bearing joints (hemophilic arthropathy)
Repeat episodes of bleeding
Where is bleeding MC in hemophilia A&B
Joints (hemarhtrosis; severe if spontaneous) muscles skin GI GU
Labs for Hemophilia A will show
Platelets and PT: normal!
aPTT: prolonged (indicative of intrinsic pathway, factor VIII)
How do you manage hemophilia A
Factor VIII concentrate infusions
Desmopressin (increases release of vWF to help clot)
-Pt ed: avoid trauma, high risk activity, ASA, and go to genetic counseling
What are dysfunctional platelets
Congenital (abn vary) or Acquired (MC; drugs, alcoholism, myeloproliferative)
Lab studies for dysfunctional platelets will show
normal count
normal morphology
prolonged bleeding time
-nothing is wrong with the amount or the shape, but they just don’t work!
How do you manage platelet dysfunction
dc offending agent
hemodialysis in uremic cases
platelet transfusion if serious bleeding
What is splenic sequestration
Splenomegaly/hypersplenism: Thrombocytopenia
Post-splenectomy: reactive thrombocytosis
What causes increased destruction of platelets
ITP: autoimmune destruction of platelets
What causes increased consumption of platelets
TTP
HUS
DIC
What is ITP
Antibody mediated destruction of platelets causes reduced PLT lifespan
Primary: 2/2 AI mechanisms leading to PLT destruction and underproduction NOT triggered by an associated condition
Secondary: associated with another condition (hepatitis, SLE, HIV, CLL)
Explain acute vs chronic ITP
Acute: self limited, MC in kids, IgG associated, preceded by viral URI
Chronic: MC in females, peak at 20-50, insidious onset, associated w/ other AI dz or HIV
What are clinical features of ITP
ASx! or Petechiae, purpura, hemorrhagic bullae on skin Epistaxis, oral bleeding, menorrhagia SAH, ICH *NO splenomegaly*
Lab studies for ITP may show
Thrombocytopenia (<20)
Coag studies are normal
Bone marrow may show increased megakaryocytes
Diagnosis of exclusion
How do you manage ITP
Avoid PLT antagonists (NSAIDs, ASA)
Acute: resolves spontaneously
Chronic: high dose prednisone or DXM. IVIG. Refractory? splenectomy or Danazol
Emergency: stop bleeding and give platelet transfusion
Why is platelet transfusion not a long term Tx in ITP
Because the body’s natural response to any platelet it to destroy it. So if you put more in, they will help acutely, but eventually the body will attack!
You need to get to the root of the problem! the spleen
What is heparin induced thrombocytopenia (HIT)
Life threatening complication of exposure to heparin
Results from auto-AB against endogenous platelet 4 in complex with heparin
Removal of IgG coated platelets by macrophages
Associate with arterial and venous thrombosis (hypercoagulable)
How do you manage HIT
D/C HEPARIN!! switch to a different anticoag
What is TTP
Rare, often fatal, MC idiopathic disorder affecting 20-50 y/o females > males
How does TTP present
Abrupt onset (acute, chronic, or relapsing)
Fever, fatigue, abdominal pain (pancreatitis)
*HA, AMS, FND that wax and wane
skin pallor, petechiae, purpura, jaundice
What happens in TTP
Microangiopathic hemolytic anemia + Thrombocytopenia
Endothelial layer of small vessels is damaged= fibrin deposition and plt aggregation
As RBC travel thru damaged vessels they’re fragmented= intravascular hemolysis
What is hemolytic uremic syndrome
Looks identical to TTP (microangiopthic hemolytic anemia + thrombocytopenia)
Rapid RBC destruction causes renal insufficiency, also due to obstruction of small renal arteries
MC in infants and kids after an E. Coli infection
You can tell it’s HUS and not TTP because
HUS lacks neurologic findings (TTP has HA, AMS, FND)
Also, HUS has more associated renal problems (TTP does not)
TTP has fever, HUS does not
How does HUS present
abdominal pain and bloody diarrhea x 5-10 days
Anemia, thrombocytopenia, fatigue (like TTP)
Labs for TTP and HUS will show
Microangiopathic hemolytic anemia: Reticulocytosis, increased LDH and indirect bili, Negative Coomb’s test
Thrombocytopenia
Schistocytes (helmet cells) on peripheral smear
Normal coag tests
Renal insufficiency
How can you tell it’s TTP and not DIC
DIC will have all abnormal coagulation tests! TTP has normal ones
How do you manage TTP-HUS
Adults: Corticosteroids! also Plasmapheresis, and if refractory try Rituximab
Kids: IVF, electrolyte repletion
(high risk mortality in adults)
What is DIC (disseminated intravascular coagulation)
Potentially life threatening condition where proteins that control blood clotting become overactive
Typically associated with a severe underlying systemic illness
What are the steps in DIC
1: Extensive thrombosis
2: clotting factors and platelets are used up= bleeding and hemorrhage
Essentially widespread platelet consumption
What is the MOA of DIC
Widespread activation of coagulation cascade
increased fibrin clots that entrap platelets
Microthrombi cause RBC destruction and small vessel occlusion
Massive consumption of platelets, fibrin, and coag factors
uncontrolled bleeding
Clinical conditions associated with DIC are
Sepsis Trauma Cancer Obstetric complications Vascular d/o (giant hemangioma) Reaction to toxins (snake venom) Immune d/o (allergic rxn, hemolytic transfusion, transplant rejection)
How does DIC present clinically
Bleeding > Clotting
Multiple organ systems
Origin of hemorrhage usually microvascular (petechiae, GI, lung, obstetrics)
Hallmark: Bleeding from IV site or surgical wound!
Labs for DIC will show
Decreased platelets and fibrinogen
Increased PT and PTT
Increased fibrinolysis= increased fibrin degradation products
Increased D-dimer (sensitive to fibrin degradation products)
Microangiopathic hemolytic anemia
Schistocytes on peripheral smear
How do you manage DIC
Quick recognition, Aggressive Tx
Transfusion: Cryoprecipitate (fibrin replacement), FFP (coag factors), Plt, RBC
-If triggered by a specific condition, treat the condition and it may resolve
What is vW disease
Autosomal dominant congenital coagulopathy
Reduced levels of factor VIII antigen or ristocetin factor
6 major types, type 1 MC
All types have vWF deficiency
Acquired may be 2/2 bone marrow malignancy, valproic acid, or SLE
vWF serves two main functions
Facilitates platelet adhesion by linking plt membrane to vascular subendothelium
Plasma carrier for factor VIII
SO: low vWF= bleeding
How does vW disease present
Bleeding
Spontaneous hemarthrosis and soft tissue bleed (not as common as in hemophilia)
Bleeding worse with ASA
Bleeding decreases with estrogen and pregnancy (hypercoagulable states)
Labs for vW disease may show
Prolonged bleeding time (bleeding time is normal in hemophilia) Low vWF (confirmation test) INR normal
How do you manage vW disease
Desmopressin for type 1 (increases vWF release!) Factor VIII infusion Humate P (derived from human plasma, has factor VIII and vWF)
