Thrombocytopenia

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What are the broad causes for thrombocytopenia?

Production failure:
- Bone marrow isn't producing platelets because of malignancy/fibrosis/other
Destruction of megakaryocytes:
- Chemotherapy
- large amounts of EtOH
Reduced thrombopoetin:
- advanced liver disease
Platelet "trapping":
- An enlarged spleen can sequester too many platelets (over 1/2) and reduced the number available for circulation

What are the specific types of consumptive thrombocytopenia?

- Disseminated Intravascular Coagulation (DIC)
- Thrombotic thrombocytopenic purpura (TTP)
- Hemolytic uremic syndrome (HUS)
- Drug-induced Immune Thrombocytopenia
- Heparin induced thrombocytopenia (HIT)
- Idiopathic thrombocytopenic purpura (ITP)
- Neonatal Alloimmune Thrombocytopenia (NAIT)

What is DIC (Disseminated Intravascular Coagulation)?

Unregulated coagulation system that leads to both the activation of clotting factors and fibrinolytic system
- Consumption of coagulation factors and platelets
- Can present as clotting or bleeding , and can be acute or chronic
- Many different causes with a common clinical/lab picture

What are the acute and chronic causes of DIC?

Acute DIC:
- sepsis
- OB emergency
- trauma, burns, poisons/venoms
- acute pancreatitis
- severe hemolysis (sickle cell crisis)
Chronic DIC:
- cancer
- vasculitis
- liver disease

How do you treat DIC?

- Treat the underlying condition first!!!
- If absolutely necessary, treat those patients with significant bleeding or clotting
"fuel to the fire" hypothesis

What are the characteristic lab findings in DIC?

- Abnormal PT, PTT and TT / fibrinogen tests (often, but not always)
- Platelet count is often low (beware movement within the normal range- watch trends)
- D-dimer should be very high (lots of clotting)
- Can see multiple schistocytes on examination of peripheral smear (1 or 2 can be normal)
- More likely to have abnormalities in acute DIC vs. chronic DIC (the body has time to compensate)

What is Microangiopathic Hemolytic Anemia?

Anemia due to hemolysis of RBCs caused by physical shear damage in capillaries
- DIC
- TTP
- HUS
- Miscellaneous

What potentially lethal condition should you check for if a patient has: Low RBCs, low platelets, increased creatinine (impaired liver function), fever, and neurologic deficits?

Thrombotic Thrombocytopenic Purpura (TTP):
Most patients do not have all 5 at presentation, but if you let them sit in the ED long enough, they will develop all 5 (unless they die first)

What is the underlying cause for thrombotic thrombocytopenic purpura (TTP)?

- Problem with vWF (specifically low ADAMKTS-13 activity)
Normally:
- vWF is secreted by endothelial cells in very long chains
- Once in circulation, vWF cleaving protease (ADAMTS-13) cuts it into smaller pieces
- Very long vWF is extra-sticky and can cause platelets to spontaneously aggregate
- Putative diagnosis of TTP requires demonstration of decreased ADAMTS-13 activity

How do you treat thrombotic thrombocytopenic purpura (TTP)?

Unless the patient is in the process of bleeding to death, DO NOT transfuse platelets!!!!
Transfused platelets will quickly be consumed to make more clots thus worsening of symptoms

- Plasma exchange (not transfusion) to replace ADAMTS-13

How is hemolytic uremic syndrome (HUS) different than TTP?

Presents almost identically to TPP, except:
- Renal damage usually prominent without significant neurologic abnormalities
- Most often affects children following viral or bacterial infection (E. coli O157:H7 produces shiga-like toxin)
- Given right symptoms, diagnosis of exclusion (maybe can culture O157:H7)

How do you treat HUS?

- Similar to TTP, if you transfuse platelets you run the risk of increasing thrombosis
- Usually supportive care because the condition is self-limited (unlike TTP where almost all will die without plasma exchange)

What is drug-induced thrombocytopenia?

- any medication can trigger an autoimmune reaction to platelet-drug complexes
- Notorious ones include quinine, quinidine, salicylates, thiazides, sulfa drugs
- Moderate thrombocytopenia (50k) as opposed to HUS and TTP (20K-40K)

How do you treat drug-induced thrombocytopenia?

- stop as many drugs as possible when faced with thrombocytopenia
- Recovery after withdrawal makes diagnosis
**Very similar to drug-induced hemolytic anemia

Is it normal for people on heparin to have low platelets?

Maybe:
- Usually a small and predictable drop with no other signs or symptoms in people getting heparin treatment

However, a large drop in platelets (20K- 50K) that is not as immediate (4-7 days after) may indicate Heparin- Induced Thrombocytopenia (HIT) which is not normal

How prevalent is Heparin- Induced Thrombocytopenia (HIT)? How can it present?

< 1% of people starting heparin therapy

- Can present with thrombosis or bleeding after starting heparin
- There is a precipitous drop in platelet count (20-50k)

Note: If the patient has received heparin before, the response can be more rapid (1-3 days)

What is the underlying cause of Heparin- Induced Thrombocytopenia (HIT)? Treatment?

- Caused by an autoantibody to heparin+platelet
- IMMEDITATELY stop all heparin (even LMWH) if HIT is even suspected
- Unless the patient is in the process of bleeding to death, DO NOT transfuse platelets until all the heparin is out of their system (~1 day)
- Switch to DTI (direct thrombin inhibitors) therapy if anticoagulation needed
- After the heparin has been stopped for several hours, draw a sample to send to lab for detection of antibody
**If really HIT, platelet count should return to normal in a few days after ALL heparin has been removed

What is the underlying cause of Idiopathic Thrombocytopenic Purpura? How low of a platelet count for ITP?

- Autoantibody which attaches to platelets
- Platelet count can be fairly low (10-20k), but spontaneous bleeding is rare

How do you treat ITP (Idiopathic Thrombocytopenic Purpura)?

- If not significantly bleeding, do not need platelet transfusion
- Unlike other conditions, platelet transfusion should not hurt the patient, but usually does not raise the platelet count
- Treat with immunosuppression (steroids, other agents) and / or splenectomy

What is the underlying cause of Neonatal Alloimmune Thrombocytopenia?

- If baby has different platelet antigens from mother, then mother can make antibody to baby's platelet antigen
- Maternal antibodies then kill baby's platelets
***This can happen on the 1st pregnancy, and there is no screening for it

What do you worry about if a baby has Neonatal Alloimmune Thrombocytopenia?

With low numbers (10-20K) there is a risk of intracranial hemorrhage

How do you treat Neonatal Alloimmune Thrombocytopenia?

- If necessary, treat with transfusion of washed, maternal platelets (not just platelets from standard donor)
- Very similar to hemolytic disease of the newborn

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