PLATELET DISORDERS

All platelet disorders have increased bleeding time and mucus membrane bleeding (epistaxis, petechiae). The INR, PT and PTT will be normal. 

With QUANTITATIVE disorders there are less platelets (thrombocytopenia)

IMMUNE THROMBOCYTOPENIC PURPURA (ITP) - the body’s immune system makes IgG against the Gp2b3a receptor on platelets. The spleen then gobbles up the opsonized platelets. It’s usually idiopathic or secondary to lupus, HIV, CLL or drugs. Give Rituximab (B-cell CD20 blocker) or steroids to decrease inflammation. Give IVIG to help with severe cases. Perform a splenectomy for refractory cases (spleen is both an Ab factory and a platelet eater).  Kids can get acute ITP weeks after a virus/vaccine, it’s mild and self-limiting. 

THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP) - “Thrombotic” (the patient has clots) “Thrombocytopenic” (the platelets are consumed making clots) “Purpura” (they have purpura). The patient lacks good ADAMTS13 enzymes, which chop up the vWF that are glued together in storage so that they can be degraded. Without ADAMTS13, the vWF multimers enter the bloodstream during trauma. vWF multimers cause weird platelet adhesion patterns, resulting in microangiopathic hemolytic anemia and purpura. TTP is usually due to autoimmune production of ADAMTS13 antibodies. Do plasmapheresis to filter out their bad antibodies, then give steroids and Rituximab to block the synthesis of new ones. Mortality is quite high, unfortunately. 

HEMOLYTIC UREMIC SYNDROME (HUS) - Kid eats uncooked beef infected with E. coli 0157:H7. It causes bloody diarrhea, and releases a verotoxin, which damages endothelium. Microthrombi form there. Tends to affect the kidney. The microthrombi cut up RBCs (schistocytes) and block flow to the kidney (uremia). The child develops acute kidney injury. Self limiting.

With QUALITATIVE disorders there are plenty of platelets (no thrombocytopenia), but the darn things won’t work

VON WILLEBRAND DISEASE - the most common genetic bleeding disorder. This is an Autosomal Dominant condition that disables von Willebrand Factor. vWF is primarily involved in primary hemostasis (glues Gp1b to the subendothelium), but it also plays a role in secondary hemostasis (stabilizes Factor 8). This makes it primarily look like a qualitative platelet disorder, but since it impacts the coagulation cascade via Factor 8, you can see an increased PTT. In the lab, add Ristocetin (a vWF analog) to their blood. If it doesn’t clot, they may have vWD. Treat with Desmopressin (increases vWF release from Weibel-Palade bodies of endothelial cells). It’s common and mild. 

BERNARD-SOULIER SYNDROME - Genetic condition affecting the Gp1b receptor on platelets. They can’t adhere. The platelets end up looking large for some reason. There is 1 “B” in “Bernard-Soulier Syndrome”

GLANZMANN THROMBASTHENIA - Genetic condition affecting the Gp2b3a receptor on platelets. They can’t aggregate. Difficult to pronounce and starts with G, just like Gp2b3a.

ASPIRIN - Drops TXA2 by irreversibly inhibiting COX 1/2, which stops platelets from expressing Gp2b3a and aggregating for the rest of their short lives. 

UREMIA - Nitrogenous waste builds up in kidney disease, which messes up adhesion and aggregation somehow.