The differential diagnosis for thrombocytopenia is broad. In the setting of infection, disseminated intravascular coagulation (DIC) should always be investigated but is fortunately rare. See the chart below for other causes of thrombocytopenia. This patient was diagnosed with thrombotic thrombocytopenic purpura (TTP). See the highlighted area of the chart.
If TTP is suspected, one should order an ADAMTS13 activity level. This is obviously a send-out lab, and the patient's came back undetectable at <5% (normal >66%). Severe deficiency of ADAMTS13 activity (<10%) may be acquired or congenital and is relatively specific for TTP. Severe ADAMTS13 deficiency is observed in approximately two-thirds of patients with idiopathic TTP.
TTP is a rare but potentially life-threatening condition that should be suspected whenever there is evidence of thrombocytopenia associated with microangiopathic hemolytic anemia (MAHA). The classic pentad includes fever, renal insufficiency, low platelets, hemolysis, and CNS involvement. Gastrointestinal symptoms such as abdominal pain, vomiting, and diarrhea are also common. Coagulation studies should be normal. If they are not, DIC should be suspected or at least considered.
TTP is often caused or triggered by an underlying medical condition or medication. In this patient, the trigger appears to have been a pharyngeal infection. Other triggers include pregnancy, autoimmune diseases, and a number of medications. See the chart for more information on the triggers, clinical presentation, lab abnormalities, and complications of TTP.
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Treatment of TTP involves treating or avoiding any triggering conditions, as well as urgent plasma transfusion followed by plasmapheresis in an ICU setting in consultation with a hematologist. Platelets transfusion should generally be avoided, because it has the potential to make matters worse. Platelets are only typically given if there is life-threatening bleeding. Other treatments for TTP may include platelet inhibitors such as aspirin, steroids, and dialysis if renal function is severely affected.
Brady Pregerson, MD, is an emergency physician at Cedars-Sinai Medical Center in Los Angeles and at Tri-City Medical Center in Oceanside, California.
Pregerson B. Emergency Medicine1-Minute Consult Pocketbook. 5th ed. EMresource.org; 2017.
A Diagnostic Consensus
Like the patient herself, her doctors assumed all her symptoms were connected to the can she’d dropped on her foot. Why hadn’t that injury healed? And why was the entire right leg — and some of the left — so painful? None of the tests conducted in her nearly two weeks in the hospital explained it. Eventually her first Mass General doctors concluded that she had an unusual disorder called complex regional pain syndrome (C.R.P.S.). This disorder, which usually affects a limb after some trauma, is thought to be caused by injury to the nervous system. That damage in turn causes pain, swelling and changes in skin color and temperature. No one knows why the body has this extreme overreaction. Treatment has to focus on reducing pain rather than on treating the disorder. Recovery takes months, even years. Having made this diagnosis, the doctors sent the patient home to follow up with specialists to treat the pain.
In the days after this second hospitalization, the patient worsened. She felt exhausted and cold all the time. One morning upon waking, she felt so weak and tired that she couldn’t stand. She scooched herself along the floor toward the bathroom. Halfway there, she was so incapacitated that she lay down and called her sister. I think I’m dying, she told her. Her hand dropped weakly to the floor. Her sister asked for 911, and the E.M.T.s came and took her to the emergency room for the third time.
Loss of Blood
A blood test showed that she was bleeding internally again. She had less than half the blood she should have in her circulatory system. No wonder she was cold and tired and out of breath — these are classic signs of severe anemia. She was given more blood and then transported back again to Mass General.
As Naranbhai read through the records, he compiled a list of diseases that could bring this woman to the hospital three times over a month with severe pain and blood loss. It was a scary collection. At the top were cancers that could keep her from making blood. Next: diseases that interfered with her body’s ability to form clots and stop bleeding. All were terrible possibilities.
Dr. Leigh Simmons, the internist supervising Naranbhai, usually waited to see patients until after the resident developed his own thoughts about the case. But it was late, and this patient sounded particularly sick, so Simmons and Naranbhai went to visit the patient together.
Seeing the Patient Anew
She was a small woman, quite thin and pale beneath a dark Mediterranean complexion. Her 15-year-old daughter stood holding her hand. Simmons introduced herself and then stepped back to let Naranbhai lead the investigation. Rather than focus his questions on her foot and leg, he cast a much wider net. Tell me everything that’s going on, he asked. She’d had her period for nearly a month now, the woman said. That had never happened before. And, her daughter added, she had these weird dots on her legs. They just popped up a few weeks before. Naranbhai looked carefully at the mother’s legs. They were covered with tiny freckle-size dots of blood trapped under the skin at the hair follicles.
Naranbhai looked at Dr. Simmons. Was she thinking what he was thinking? He looked back at the patient. Did her gums ever bleed when she brushed her teeth, he asked. All the time, she exclaimed.
Can I see? the young doctor asked. Her gums were swollen and beefy red. He felt as if they might start bleeding just by looking at them. He looked up to Simmons, who smiled back encouragingly. He knew what she had. And so did Simmons.
Clues in the Diet
What kind of foods do you eat? he asked. Every morning she had two scrambled eggs. For lunch she had tuna on crackers. And for dinner she had more scrambled eggs and rice. Did she ever eat any fruits or vegetables — especially oranges or lemons? Never, she told him. They gave her wicked heartburn.
She had something known as gastroparesis, she explained. Her stomach and intestines didn’t move food forward normally, and so food stayed in her stomach for hours. When food moves that slowly, you have to be careful that what you eat agrees with you.
No citrus for years. It was clear to Naranbhai that this modern woman had an ancient disease. She had scurvy — a disorder caused by a severe deficiency of vitamin C.
In the mid-18th century, a naval surgeon named James Lind proved that the juice of oranges and lemons would cure the bony aches, strange bleeding and sudden death of sailors afflicted with the illness, and the British Navy later mandated the use of lemon juice on all vessels. But it wasn’t until the 20th century that researchers recognized that the cause of scurvy was the lack of a certain nutrient, which they named vitamin C. Without this organic chemical, new connective tissue, essential for the repair or replacement of damaged or dying cells, cannot be made, and that causes the bleeding, the bruising, the telltale little red dots and the terrible fatigue. Our bodies can’t make vitamin C, and so we rely on the foods we eat to provide it. Avoiding these foods — as this woman did — can deplete the body’s supply in just a few months.
The Miracle of Vitamin C
The doctors sent off a blood test to measure her vitamin C, and they started the woman on large doses of the required vitamin. The improvement was almost immediate: her gums stopped bleeding within days; her bruises started to turn yellow and fade. And she started to feel stronger and less fatigued.
That was two months ago. Now she feels great. She still can’t eat oranges. But she takes her vitamin C tablets every single day.Continue reading the main story